Strength and muscle mass development after a resistance-training period at terrestrial and normobaric intermittent hypoxia.

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.

Acute physiological responses to low-intensity blood flow restriction cycling.

OBJECTIVES: Blood flow restriction (BFR) during interval cycling may stimulate aerobic and anaerobic adaptations. However, acute physiological responses to BFR interval cycling have not been extensively investigated. DESIGN: Eighteen males completed low-intensity (LI), low-intensity with BFR (LIBFR) and high-intensity (HI) interval cycling sessions in randomised and counterbalanced order. These included a standardised warm-up and three two-min intervals interspersed with two-min recovery. Interval intensity during HI, LI and LIBFR were 85%, 40% and 40% of peak power output obtained during graded exercise tests. METHODS: During LIBFR, 80% arterial occlusion was applied to both legs during the interval efforts and removed during recovery. Continuous measures of heart rate (HR), cardiac output (CO) and oxygen consumption (V˙O2) were recorded. Blood pressure (BP) and rating of perceived exertion (RPE) were measured following intervals. Blood lactate concentration was measured pre- and post-exercise. RESULTS: BP, HR, CO, V˙O2, lactate and RPE were greatest during HI. During the active intervals, BP, HR and CO were greater during LIBFR than LI. V˙O2 during recovery periods were greater in LIBFR than LI. Post-session lactate was greater during LIBFR than LI. Importantly, mean arterial pressure during interval three was significantly greater in LIBFR (124±2mmHg) than HI (114±3mmHg). CONCLUSIONS: LIBFR increases cardiovascular and metabolic stress compared with LI and could provide an alternative aerobic training method for individuals unable to perform high-intensity exercise. However, increases in mean arterial pressure during LIBFR indicates high myocardial workload, and practitioners should therefore use caution if prescribing LIBFR for vascular compromised individuals.

Influence of alpha and gamma radiations and non-radiation risk factors on the incidence of malignant liver tumors among Mayak PA workers.

This Mayak worker-based study focuses on evaluating possible associations between malignant liver cancers and chronic alpha irradiation, chronic gamma irradiation, and non-radiation risk factors (alcohol consumption, smoking, viral hepatitis, chemical exposure, and chronic digestive diseases). This is the first multivariate study related to liver cancer among Mayak workers. The study was performed using the nested, case-control approach and includes 44 cases of malignant liver tumors diagnosed from 1972 to 1999, and 111 matched controls. Adjusted odds ratio (OR(ad)) was evaluated relative to a group of workers with alpha radiation doses to liver (D(alpha)) < 2.0 Gy. Dose estimates of D(alpha) > 2.0 Gy (corresponding (239)Pu body burden estimates >20.4 kBq) were significantly associated (p < 0.003) with the occurrence of hemangiosarcomas (HAS) but only marginal significance (0.05 < p < 0.1) was found for hepatocellular cancers (HCC). The ORad for HAS was 41.7 [95% confidence interval (CI): 4.6, 333] for a group with D(alpha) in the range >2.0-5.0 Gy and was 62.5 (7.4, 500) for a group with D(alpha) > 5.0-16.9 Gy. The attributable risk (AR) was calculated as 82%. For HCC, O(Rad) was estimated as 8.4 (0.8, 85.3; p < 0.07) for a group with D(alpha) in the range >2.0-9.3 Gy. For the indicated group, the AR was 14%. An association with high external gamma-ray doses (D(gamma)) to the total body was revealed for both HCC and for combined liver cancers when dose was treated as a continuous variable. However, we find no evidence that chronic low doses of gamma rays are associated with liver cancer occurrence. Cholangiocarcinoma (CHC) was not associated with either alpha- or gamma-ray exposure. As expected, an association between alcohol abuse and HCC was inferred [O(Rad) = 3.3 (1.2, 9); AR = 41%] but not for CHC or HAS.

Chromosomal aberrations in lymphocytes of peripheral blood among Mayak facility workers who inhaled insoluble forms of 239PU.

A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239Pu and to external gamma rays. Body burden estimates for 239Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable) among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated approximately 25 y after first contact with 239Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 +/- 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 +/- 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239Pu. No relationship between chromatid aberrations and 239Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found.

Methodologies for predicting the expected combined stochastic radiobiological effects of different ionizing radiations and some applications.

A methodology for predicting the expected combined stochastic radiobiological effects of sequential exposure to different ionizing radiations is used to arrive at a methodology for predicting the radiobiological effects of simultaneous exposure. Both methodologies require developing additive-damage dose-effect models. Additive-damage dose-effect models are derived assuming (a) each radiation comprised by the combined exposure produces initial damage called critical damage that could lead to the radiobiological effect of interest; (b) doses of different radiations that lead to the same level of radiobiological effect (or risk) can be viewed as producing the same amount of critical damage and being indistinguishable as far as the effects of subsequently administered radiation. Derived dose-effect functions that describe the risk per individual, conditional on radiation dose, are called risk functions. The methodologies allow the use of known radiation-specific risk functions to derive risk functions for combined effects of different radiations. The risk functions for combined exposure to different radiations are called global risk functions. For sequential exposures to different ionizing radiations, the global risk functions derived depend on how individual radiation doses are ordered. Global risk functions can also differ for sequential and simultaneous exposure. The methodologies are used to account for some previously unexplained radiobiological effects of combined exposure to high and low linear-energy-transfer radiations.

Pulmonary carcinogenicity of repeated inhalation exposure of rats to aerosols of 239PuO2.

To study the long-term biological effects of repeated inhalation exposure to 239PuO2, 84-day-old rats were exposed to aerosols of 239PuO2 to re-establish desired 239Pu lung burdens of 26, 80 or 250 Bq every other month for 1 year (seven exposures). Other rats were exposed once at 84 or 450 days of age to achieve desired initial lung burdens of 30, 90, 280 or 850 Bq. The incidences of lung tumors were not significantly different (Fisher's exact test; P > 0.05) in groups of rats with similar lifetime mean alpha-particle doses to the lungs of 0.90 +/- 0.39 to 4.4 +/- 1.8 (+/- SD) Gy, whether exposed once or repeatedly. Among rats with mean alpha-particle doses of 12 +/- 2.4 to 10 +/- 2.1 Gy to the lungs after single or repeated exposures, respectively, the crude incidence of lung tumors was significantly less (Fisher's exact test; P < 0.05) in the rats exposed repeatedly. Times to death of rats with lung tumors were compared among groups with similar alpha-particle doses to the lungs after single or repeated exposure to 239PuO2. Those that died with lung tumors after repeated exposures died at times similar to (Mantel-Cox statistic; P > 0.05) or later than (Mantel-Cox statistic; P < 0.05) those for 84-day-old rats exposed once. The risk of lung tumors in rats per unit dose to the lungs was less in the rats exposed repeatedly than in those exposed once. It was concluded that alpha-particle doses to the lung of rats exposed repeatedly to aerosols of 239PuO2 were not more carcinogenic and possibly were less carcinogenic than the dose after a single inhalation exposure when rats with similar lifetime alpha-particle doses to the lungs were compared. The relative biological effectiveness in rats of the alpha-particle dose to the lungs from inhaled 239PuO2 relative to beta-particle doses to the lungs from inhaled 144CeO2 was 21 +/- 3.

Toxicity of inhaled plutonium dioxide in beagle dogs.

This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.

The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells.

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.

A biological-based model that links genomic instability, bystander effects, and adaptive response.

This paper links genomic instability, bystander effects, and adaptive response in mammalian cell communities via a novel biological-based, dose-response model called NEOTRANS3. The model is an extension of the NEOTRANS2 model that addressed stochastic effects (genomic instability, mutations, and neoplastic transformation) associated with brief exposure to low radiation doses. With both models, ionizing radiation produces DNA damage in cells that can be associated with varying degrees of genomic instability. Cells with persistent problematic instability (PPI) are mutants that arise via misrepair of DNA damage. Progeny of PPI cells also have PPI and can undergo spontaneous neoplastic transformation. Unlike NEOTRANS2, with NEOTRANS3 newly induced mutant PPI cells and their neoplastically transformed progeny can be suppressed via our previously introduced protective apoptosis-mediated (PAM) process, which can be activated by low linear energy transfer (LET) radiation. However, with NEOTRANS3 (which like NEOTRANS2 involves cross-talk between nongenomically compromised [e.g., nontransformed, nonmutants] and genomically compromised [e.g., mutants, transformants, etc.] cells), it is assumed that PAM is only activated over a relatively narrow, dose-rate-dependent interval (D(PAM),D(off)); where D(PAM) is a small stochastic activation threshold, and D(off) is the stochastic dose above which PAM does not occur. PAM cooperates with activated normal DNA repair and with activated normal apoptosis in guarding against genomic instability. Normal repair involves both error-free repair and misrepair components. Normal apoptosis and the error-free component of normal repair protect mammals by preventing the occurrence of mutant cells. PAM selectively removes mutant cells arising via the misrepair component of normal repair, selectively removes existing neoplastically transformed cells, and probably selectively removes other genomically compromised cells when it is activated. PAM likely involves multiple pathways to apoptosis, with the selected pathway depending on the type of cell to be removed, its cellular environment, and on the nature of the genomic damage.

Systems and results of tests for chemical induction of mitotic malsegregation and aneuploidy in Aspergillus nidulans.

In Aspergillus several types of test systems have been developed for detection of chemicals which induce aneuploidy and/or malsegregation of chromosomes. Results from 23 papers were reviewed in which numerical data for 42 chemicals had been reported. The test systems fall into two groups. One group includes all purely genetic tests that detect euploid mitotic segregants from heterozygous diploids and identify these either as products of malsegregation of chromosomes or as products of crossing-over (13 papers, several reviewed in detail previously; Käfer et al. (1982) and Scott et al. (1982)). The other group includes tests that treat haploid or diploid strains and detect aneuploids as unstable abnormally growing segregants which can be identified as specific disomics or trisomics by their characteristic phenotypes. In addition, such tests characterize abnormal segregants from heterozygous diploids by correlating phenotypes with patterns of genetic segregation in spontaneous euploid sectors. This analysis makes it possible to distinguish between induced primary aneuploidy of whole chromosomes and partial tri- or monosomy resulting from chromosome breakage and secondary spontaneous malsegregation (10 papers). Based on results of both types of tests, it is postulated that chemicals which cause increases of euploid malsegregants, but not of crossovers, normally induce aneuploids as primary products (as shown for 7 of the 14 cases). These include compounds which damage spindles or membranes (especially the well-known haploidizing agents) and generally are effective only when growing cells are exposed. (8 chemicals that may belong in this category could not be classified for certain, because information was insufficient.) On the other hand, chemicals which cause increases of all types of euploid segregants (11 cases), mostly induce drastic mutations and aberrations as primary effects and cause spontaneous malsegregation or crossing-over only as secondary events (as demonstrated for radiation-induced abnormals). In addition, a few chemicals were negative, because they increased only crossing-over or showed no increased segregation at all at concentrations which reduced survival or growth rate (9 cases). Recommendations are made for standardization of methods and protocols. New tester strains and specific procedures are outlined which should be useful for conclusive tests of chemicals that may induce aneuploidy.

UV mutagenesis in inhibitor depleted conidia of Aspergillus nidulans.

UV treated conidia of a strain of Aspergillus nidulans (meth Gl. biAl) depleted of germination inhibitory substances have been examined for inactivation and mutation induction at groups of suppressor gene loci defining three classes of methionine revertants. An exponential decline in the colony forming ability and quadratic increase in mutation frequency (for each class of revertant) as the incident dose increased were observed. The induced mutation frequency for each class and the loss of colony forming ability of the conidia are greater in the absence than in the presence of these self-inhibitors of germination. However, the relative frequencies of the individual classes of revertants did not differ whether the inhibitory substances were present or not. Liquid holding effects leading to increases in survival and mutation have been observed, but the relative frequencies of the individual revertant classes remain unchanged.

The induction of mutations to 2-thioxanthine resistance in inhibitor depleted conidia of Aspergillus nidulans by gamma-radiation in the presence of oxygen or nitrogen.

A strain of Aspergillus nidulans has been used to study the inactivating and mutagenic effect of 60Cogamma-rays in the presence of oxygen or nitrogen. Mutation was studied by the 2-thioxanthine system which selectively detects forward mutation at a number of gene loci (at least 16). Mutants resistant to conidial pigmentation effects of 2-thioxanthine can be divided into four main classes (2TxR, hx, uaY and cnx) and three of these classes (hx, uaY and cnx) can be further characterized at the gene level. The results demonstrate the existence of a marked differential forward mutational response of gene loci in Aspergillus conidia which is dependent upon whether gamma-irradiation in aqueous suspension was carried out in the presence of oxygen or of nitrogen: this effect is independent of the dose of radiation exposure. The specificity for mutation is altered by the presence of the self-inhibitor of germination for the anoxic treatment but not the oxic irradiation. The implication of different oer's (oxygen enhancement ratios) for mutation induction in different classes or genes for the mechanism and type of damage induced by the two radiation conditions are discussed.

Chemical and biological characterization of hazardous industrial waste. II. Eukaryotic bioassay of a wood-preserving bottom sediment.

The eukaryotic haploid and diploid forms of Aspergillus nidulans were used to detect gene mutations and various types of chromosome damage, respectively, in the acid, base and neutral fractions of a wood-preserving bottom sediment. The corresponding response to prokaryotic mutagenicity assays and major chemical constituents of the 3 waste fractions were described by Donnelly et al. (1987). The haploid methionine system detected genotoxic compounds in all 3 primary waste fractions without metabolic activation. With metabolic activation, the maximum response observed in the gene mutation assay was induced by the base fraction. In the diploid assay without metabolic activation, the acid fraction induced the maximum number of major chromosome abnormalities, while the base fraction induced the maximum number of minor deletions or insertions. These results appear to reflect the different composition of the waste fractions since each fraction induced a different type of genetic damage in the two bioassays employed. Alternately, because exposure in the diploid assay was during a growth stage, the results may reflect a varying response at different points of the cell division cycle. The results obtained using eukaryotic bioassays indicate that the wood preserving waste contains compound(s) capable of inducing point mutations, chromosome damage, recombination, and compound(s) acting as spindle poisons.

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Models for estimating the risk of ulcers in the small intestine after localized single or fractionated irradiation.

Subacute and chronic ulcerations of the intestinal mucosa are important causes of serious complications following radiation therapy for abdominal or pelvic tumours. We describe dose-response models for estimating the risk of mucosal ulcers in the small intestine after uniform, localized single or fractionated (once-daily) X-ray exposure. The models were fitted to data for ulceration incidence, based on a 26 week post-irradiation follow-up of male Sprague-Dawley rats which received a wide range of single and fractionated once-daily 250 kV X-ray doses to a short loop (partial volume) of transposed, but functionally intact, small intestine. The models presented for single (Weibull (W)) and fractionated (modified Weibull (MW)) exposures of a partial volume of tissue allow estimation of the risk of radiation-induced injury. While the W model is not new, its adaptation to partial volume irradiation and the MW model are. Isoeffect relationships are presented for the uniform fractional dose Ds(i%) associated with an i% (e.g. 0%, 5%, 10%, 50%) risk of intestinal mucosal ulcers as a function of the number of once-daily dose fractions, where Ds(0%) represents the threshold fractional dose. Although the Ds(5%) and Ds(0%) estimates provided for intestinal mucosal ulcers are based on animal data, the ratio Ds(0%)/Ds(5%) and more generally ratios Ds(j%)/Ds(i%) (where i not equal to j), are presumed to apply to humans. The indicated ratios are predicted to be independent of the partial volume irradiated and the number of once-daily dose fractions, and may be independent of radiation quality. Isoeffect equations are also presented that apply to circumstances where different partial volumes within the same reference volume (i.e. the total volume of tissue considered) receive different doses, but the dose within a given partial volume is uniformly distributed. These isoeffect equations provide a means of converting non-uniform dose within a reference volume to uniform isoeffect dose to the total reference volume and may have applications outside the field of radiation therapy (e.g. evaluating effects of non-uniform exposure of the small intestine or skin by a hot particle).

Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.

Mutagenicity of three agricultural soils.

A chemical and biological testing protocol was employed to evaluate the mutagenic potential of the organic compounds extracted from three agricultural soils. The analytical procedures used included bioassays with Salmonella typhimurium and Aspergillus nidulans for the detection of point mutations and a gas chromatography/mass spectrometry/computer system to identify major organic constituents. The extracts of all three soils exhibited mutagenic response in the bioassays. At a dose level of 1000 micrograms per plate, the organic extract of the Bastrop clay induced 434 net revertants; while at the same dose level the Norwood sandy clay and the Sassafrass sandy loam induced 35 and 178 net revertants, respectively, in the Salmonella assay with metabolic activation. In the Aspergillus assay, the extract of the Norwood and Bastrop soils induced a positive response without metabolic activation; this effect was reduced or eliminated in the presence of metabolic activation. Chemical analysis identified a variety of initiators, promotors, inhibitors, and cocarcinogens; however, there were no mutagenic compounds identified in any of the soil extracts. The results of this combined testing protocol indicate that the agricultural soils tested had an inherent level of mutagenic activity, which was not detected by GC/MS analysis alone, and this activity may be related to the past history of agricultural practices, including biocide applications, fertilization, and cultivation.

Respiratory tract deposition efficiencies: evaluation of effects from smoke released in the Cerro Grande forest fire.

Forest-fire smoke inhaled by humans can cause various health effects. This smoke contains toxic chemicals and naturally occurring radionuclides. In northern New Mexico, a large wildfire occurred in May 2000. Known as the Cerro Grande Fire, it devastated the town of Los Alamos and damaged Los Alamos National Laboratory (LANL). Residents were concerned about the possible dissemination of radionuclides from LANL via smoke from the fire. To evaluate potential health effects of inhaling radionuclides contained in the smoke from the Cerro Grande Fire, it was first necessary to evaluate how much smoke would deposit in the human respiratory tract. The purpose of this study was to evaluate respiratory-tract deposition efficiencies of airborne forest-fire smoke for persons of different ages exposed while inside their homes. Potential non-radiological health effects of a forest fire are reviewed. The deposition efficiencies presented can be used to evaluate in-home smoke deposition in the respiratory tract and expected radionuclide intake related to forest fires. The impact of smoke exposure on firemen fighting a forest fire is quantitatively discussed and compared. They primarily inhaled forest-fire smoke while outdoors where the smoke concentration was much higher than inside. Radionuclides released at the LANL site via the Cerro Grande Fire were restricted to naturally occurring radionuclides from burning trees and vegetation. Radiation doses from inhaled airborne radionuclides to individuals inside and outside the Los Alamos area were likely very small.

A radiation protection approach to assessing population risk for threshold-type radiobiological effects.

The potential harm to a population exposed to radiation from a nuclear accident, such as the one that recently occurred at the Chernobyl plant in the Soviet Union, is of concern to many individuals. The average dose to a population is a useful index of harm (IH) only for linear, nonthreshold-type, quantal (i.e., all-or-none) effects. For such radiobiological effects, the expected harm to the population is linearly related to the average dose. However, for nonstochastic effects, it is not. An IH is proposed for threshold-type nonstochastic effects which is based on a form of the Weibull model where, at low to moderate doses, the individual risk at dose X = D/D50 is given by the approximation Risk = ln(2)XV; where D50 is the absorbed radiation dose that produces the specified effect in one-half the population, D is the absorbed radiation dose, and V is a positive parameter. The dose, X, is in units of the D50. Use of this form of the Weibull model is limited to doses such that X is small in comparison to 1. An IH for the population can be obtained by defining a new variable, P = XV, in dimensionless units, because the individual risk is linearly related to P at low and moderate doses. The average value for P (given by [P]) for an exposed population can be used as an IH for the population when the maximum value for P does not exceed 1. Both P and [P] can be regarded as theoretical doses. The average risk for the population in terms of the average dose [P] is given by ln(2)*[P], and the expected cases of nonstochastic effects among N individuals by N*ln(2)*[P]. As an example of the application of the average dose [P], the expected cases of temporary sterility in males among the approximately 135,000 people evacuated within 30 km of the Chernobyl plant is calculated to be about 200. The cases of sterility would be expected to come from those males exposed to doses to the testes of about 0.35 Gy or higher. No cases of sterility would be expected for individuals exposed to lower doses.

Method of analysis of monotone dose-response probabilities after long-term exposure to a toxicant.

A nonparametric hazard-function (HP) method for generating monotonically increasing incidence vs dose curves after long-term exposure to a toxic agent (e.g. radiation or chemical carcinogens) is described in detail in this paper. Here, incidence refers to the response-probability estimate that is adjusted for competing risks. The maximum likelihood principle was used to arrive at an appropriate point estimate of the cumulative hazard function (i.e. the negative natural logarithm of the proportion of the nonresponders) and the response probability for an array of doses that depends on the data set to be analyzed. The resultant point estimates can be used to develop or select an appropriate model for risk vs dose assessment. As an example of the application of the HF method, data for liver neoplasms caused by long-term exposure of mice to 2-acetylaminofluorene and data for radiation pneumonitis and pulmonary fibrosis caused by long-term exposure of dogs to ionizing radiation are analyzed.