Chromosomal aberrations and SCEs as biomarkers of cancer risk.

Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.

Occupational exposure to mercury vapour on genotoxicity and DNA repair.

We have conducted a population study to investigate whether current occupational exposure to mercury can cause genotoxicity and can affect DNA repair efficiency. Blood samples from 25 exposed workers and 50 matched controls were investigated for the expression of genotoxicity. The data indicate that mercury exposure did not cause any significant differences between the workers and controls in the baseline levels of DNA strand breaks (as measured by the alkaline version of the single cell gel electrophoresis [SCGE] assay) or sister chromatid exchanges (SCE). However, the exposure produced elevated average DNA tails length in the SCGE assay and frequency of chromosome aberrations. In the studies, isolated lymphocytes were exposed to 6J/m2 UV-C light or 2 Gy dose of X-rays in a challenge assay and repair of the induced DNA damage was evaluated using the SCGE assay. Results from the UV-light challenge assay showed no difference between the workers and controls in the expression of DNA strand breaks after exposure followed by incubation in the absence or presence of the cellular mitogen (phytohemagglutinin, PHA). No difference in DNA strand breaks between the workers and controls was seen immediately after the X-ray challenge, either. However, significant differences were observed in cells that were incubated for 2h with and without phytohemagglutinin. Data from the X-rays challenge assay were further used to calculate indices that indicate DNA repair efficiency. Results show that the repair efficiencies for the workers (69.7% and 83.9% in un-stimulated and stimulated lymphocytes, respectively) were significantly lower than that of matched controls (85.7% and 90.4%, respectively). In addition, the repair efficiency showed a consistent and significant decrease with the duration of occupational exposure to mercury (from 75.7% for <10 years employment, to 65.1% for 11-20 years and to 64.1% for 21-35 years) associated with increase of cytogenetic damage. Our study suggests that the occupational exposure to mercury did not cause a direct genotoxicity but caused significant deficiency in DNA repair. Our observations are consistent with previous studies using the standard chromosome aberration assay to show that exposure to hazardous environmental agents can cause deficiency in DNA repair. Therefore, these affected individuals may have exposure-related increase of health risk from continued exposure and in combination with exposure to other genotoxic agents.

Micronuclei in peripheral blood lymphocytes and buccal epithelial cells of Polish farmers exposed to pesticides.

In this biomonitoring study, we investigated whether an occupational exposure to a complex mixture of chemical pesticides produced a significant increase of micronuclei (MN) in both peripheral blood lymphocytes and buccal cells. Forty-nine male workers exposed to pesticides, from an agricultural area of Malopolska Region in Southern Poland, together with 50 men from the same area without indication of exposure to pesticides that served as controls, were used in this investigation. No statistically significant differences in the frequencies of cytogenetic damage were detected between exposed and control individuals, for either type of cells. The multiple linear regression analysis in the case of lymphocytes indicated that the studied cytogenetic endpoints were inversely influenced by alcohol; whilst a negative binomial regression, in the case of buccal cells, indicated that the MN values were directly influenced by the ingestion of red meat. An inverse negative relationship between the cytokinesis-block proliferation index and age, and a significant increase of miscarriages due to the exposure to pesticides were also observed.

Relative biological efficiency for the induction of various gene mutations in normal and enriched with 10B Tradescantia cells by neutrons from 252Cf source.

The effectiveness of neutrons from a Californium-252 source in the induction of various abnormalities in the Tradescantia clone 4430 stamen hair cells (Trad-SH assay) were studied. A special attention was paid to check whether any enhancement in effects is visible in the cells enriched with boron ions. Inflorescences, normal or pretreated with chemicals containing boron, were irradiated in the air with neutrons from a 252Cf source at KAERI, Taejon, Korea. To estimate the relative biological effectiveness (RBE) of the beam under the study, numbers of Tradescantia inflorescence without chemical pretreatment were irradiated with various doses of X-rays. The ranges of radiation doses used for neutrons were 0-1.0Gy and for X-rays 0-0.5Gy. Following the culturing according to standard procedures screening of gene and lethal mutations in somatic cells of stamen hairs was done in the extended period, between days 7 and 19 after exposures. Maximal RBE values for the induction of pink, colorless and lethal mutations were evaluated from comparison of the slopes in linear parts of the dose response curves obtained after irradiation with X-rays and californium source. The RBE(max) value or the induction of gene mutation was estimated as 7.2 comparing the value 5.6 in the studies reported earlier. The comparison of dose-response curves and its alteration, due to changes in the cells and plants environment during and after irradiation, explains the observed differences. Inflorescence pretreated with borax responded to neutrons differently depending on the biological end points. Although, for the induction of pink mutations no significant difference was observed, though, in the case of cell lethality, pretreated with boron ion plants have shoved a statistically significant increase of the RBE value from 5.5 to 34.7, and in the case of colorless mutations from 1.6 to 5.6.

Studies on the genotoxic effects of aminophenazines using two cellular models and three different methods.

This paper presents studies on the genotoxicity of two aminophenazines: 2,3-diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP). The genotoxic activities of these compounds were evaluated with human lymphocytes using the alkaline single cell gel electrophoresis (SCGE) assay and two cytogenetic assays (chromosome aberrations (CA) and sister chromatid exchange (SCE) analysis). Results show that these chemicals elicited an increase in DNA and chromosomal damage under the studied ranges of concentration. Concentration-response curves were similar and there was a positive correlation between the damage observed at the DNA and chromosomal levels. DAP was more genotoxic than AHP and this agreed with the genotoxic potencies reported in bacterial systems.

Examination of ras oncoproteins in human plasma from healthy controls and workers exposed to petroleum emissions, including benzene-related compounds.

Ras oncoproteins in blood plasma from workers exposed to petroleum emissions and unexposed controls were examined from Polish and Estonian samples. Twenty-four workers and 35 unexposed controls were examined from Poland and 97 exposed and 40 unexposed controls from Estonia. Of the Estonian workers, 50 were exposed to benzene in a benzene production plant and 47 to polyaromatic hydrocarbons and benzene in a cokery. Blood plasma proteins were separated by gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting and detected by chemiluminescence using a monoclonal antibody as the primary antibody. There were no statistically significant differences between the exposed and the control groups in either the Polish or the Estonian samples.

[Is polycystic kidney disease a risk factor for neoplasm formation?]. / Czy wielotorbielowate zwyrodnienie nerek stanowi czynnik ryzyka zachorowania na nowotwór?

Our study aimed to elicit possible association between molecular and cytogenetic damage detected in lymphocytes of three members of family with polycystic kidney disease (41 and 19 years old females and in 9 years of age boy) and predictability to develop cancer or their susceptibility to environmental exposure. The DNA damage detected by Comet assay, chromosome aberrations and sisster chromatid exchanges were tested in lymphocytes and p21ras protein level in blood plasma. Lymphocytes of two persons showed higher level of cytogenetic damages and higher in responses to 0.5 Gy dose of radiation. We think it might be associated to specific aberration present in cells of these persons. A final conclusions can be taken when an application of FISH technique would be completed.

Monitoring of molecular and cytogenetic damage in lymphocytes from three persons with polycystic kidney disease.

BACKGROUND: Much interest has been generated in the studies that would help to understand whether there is a causal association between disease and various types of molecular or cytogenetic damage detected in human cells. MATERIALS AND METHODS: The aims of this study were to elicit the possible association between DNA and cytogenetic damage induced in lymphocytes of three members of a family with autosomal dominant polycystic kidney disease (ADPKD). The predictability to develop cancer or to sensitive response to environmental exposure of the young girl at the age of 19, her brother (9 years old) and a maternal aunt at the age of 41 were sought. Cytogenetic studies, analysis of DNA damage by single cell gel electrophoresis assay (SCGE known as a Comet assay), and analysis of p21ras protein level in blood plasma were carried out on their lymphocytes. RESULTS: The analysis for presence of chromosome aberrations in the first mitosis and sister chromatid exchanges in the second mitosis revealed elevated levels of cytogenetic biomarkers when compared to the mean values observed in the reference group in environmental biological monitoring studies. Results of sister chromatid exchanges (SCE) and percent of cells with elevated number of exchanges (high frequency cells) that were significantly higher in two probands had demonstrated susceptibility to or possibility of environmental exposure (pesticides, smoking). The results of this study show that the lymphocytes of two persons revealed increased sensitivity to 0.5 Gy dose of gamma radiation expressed in the increased, although statistically insignificant, damage detected on the molecular level after cell irradiation. CONCLUSIONS: The latter might be associated with a specific aberration present in the cells of these persons. But final conclusions can be arrived at when an application of FISH technique is completed.

Cytogenetic damage and ras p21 oncoprotein levels from patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls.

The purpose of the present communication was to determine in patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls if there was a possible association between the disease state and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors such as smoking habit and endogenous ones (sex, cancer in the immediate family) could affect these biomarkers. The individuals in all groups were as well-matched as possible for age to determine if this could be eliminated as a confounder. Peripheral blood and plasma were collected from 20 COPD patients, 31 cancer patients and 20 healthy controls. Chromosomal aberrations (CA), sister chromatid exchanges (SCE) and high frequency SCE cells (HFC) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to the confounding factors. Results were analysed by a t-test, analysis of variance (ANOVA) and stepwise multivariate regression analysis. There was an increase in CA, although not statistically so, in COPD and cancer patients by comparison with healthy controls, but there was a statistically significant increase in SCE, HFC and ras p21 oncoproteins. There was also a statistically significant difference between respiratory volume parameters in COPD patients and controls. Respiratory parameters were not measured in cancer patients. Ras p21 oncoproteins were also statistically significantly increased in the COPD and cancer patients, suggesting that the disease state alone might be sufficient to increase the oncoproteins, or that some of the COPD patients were in the process of developing cancer or perhaps some would die from COPD before cancer developed. Smoking was shown to have a marked effect on all parameters investigated. Ex-smokers showed less effects. Since age was very well controlled, there was little effect due to age. There was an effect due to sex, but cancer in the immediate family had little effect on any of the parameters.

Correlations between DNA and cytogenetic damage induced after chemical treatment and radiation.

The induction of damage in human lymphocytes has been compared after treatment in vitro with two different agents, the chemical o-phenylenediamine (o-PDA) and gamma irradiation, in the alkaline single cell gel electrophoresis (Comet) assay, and after cytogenetic analysis. The chemical treatment caused dose-related increases in DNA damage in the Comet assay and cytogenetic damage in the first and second metaphases. The results revealed a very strong association between the two types of damage. Correlation coefficients were from 0.95 to 0.97. From previous studies, high correlation coefficients of 0.99 and 0.97 in the same assays were also evaluated for X-rays and fast neutrons, respectively. On the basis of such results, we suggest that the Comet assay responses provide a good prediction of cytogenetic damage. Thus, because of its simplicity and rapidity, the Comet assay would appear to be a very useful tool for determining the genotoxicity of environmental agents.

Ras p21 protein levels in human plasma from patients with chronic obstructive pulmonary disease (COPD) compared with lung cancer patients and healthy controls.

To explore the value of an increase in ras p21 proteins in plasma as a biomarker for the carcinogenic process or for the general disease state, we have directly analysed for ras p21 proteins, plasma samples from Polish human patients with chronic obstructive pulmonary disease (COPD). They were compared with appropriate controls and also with the Polish lung cancer patients previously examined before treatment [D. Anderson, J.A. Hughes, A. Cebulska-Wasilewska, E. Nizankowska, B. Graca, Ras oncoproteins in human plasma from lung cancer patients and healthy controls, Mutat. Res. 349 (1996) 121-126]. An elevated level of ras p21 proteins was considered to be greater than 2 standard deviations (SD) above the mean negative control values. Nine out of 20 COPD patients (mean age = 65.9 years) had increased ras p21 protein levels when compared with 20 age-matched (mean age = 62.4 years) controls of the present study with a mean + 2 SD of 0.70. Eighteen out of 40 lung cancer patients (mean age = 60.1 years) had increased ras p21 protein levels compared with their concurrent controls (mean age = 40.2 years) with a mean + 2 SD of 2.53. However when compared with the age-matched controls of this present study, there were 35 out of 40 (87.5%) with increased levels. When the COPD patients and lung cancer patients were compared with 101 historical controls (age range 25-76 years, of those whose age was recorded) from unexposed healthy populations from Poland, Estonia and Spain with a mean + 2 SD of 1.83, then 4 out of 20 (20%) COPD patients and 30 out of 40 (75%) lung cancer patients had increased levels. Whether using concurrent controls, age-matched controls or historical controls, the data would suggest that an increase in ras p21 protein levels in plasma from lung cancer patients could be a possible prognostic marker or biomarker for lung cancer. COPD patients when compared with historical controls or age-matched controls had lower ras p21 protein values than cancer patients. Their ras p21 protein values might also be a biomarker for cancer. It is possible that some of these COPD patients were in the process of developing cancer or perhaps would die from COPD before cancer develops. It cannot be ruled out that the increases could be a biomarker of exposure since many of the lung cancer patients and most of the COPD patients were smokers.

Factors affecting various biomarkers in untreated lung cancer patients and healthy donors.

The purpose of the present communication was to determine in lung cancer patients and healthy donors if there was a possible association between cancer and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors (such as smoking habit) and endogenous ones (age, sex, etc.) could affect these biomarkers. Peripheral blood and plasma were collected from 31 lung cancer patients prior to treatment and 35 healthy donors of a similar socioeconomic status and from the same region in Poland. Chromosomal aberrations (CA), sister chromatid exchanges (SCE), high frequency cells (HFC), and proliferative rate index (PRI) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to confounding factors of age, sex, smoking habit, and immediate family cancer history. Results were analyzed by a t-test, analysis of variance (ANOVA), and stepwise multivariate regression analysis. All types of CA (including and excluding gaps), percent aberrant cells, SCE, and ras p21 oncoproteins were statistically significantly higher in cancer patients than in the healthy donors. Although there were smaller numbers of females in the cancer patients group who were older than the males, there was a difference due to sex (gender) with statistically significant increases in females for CA, SCE, and HFC, but there was no increase for ras p21 oncoproteins. Cytogenetic damage was not related to other cancers in the immediate families of the groups. All major CA parameters differed significantly between smokers and non-smokers in the cancer patients group, and SCE and HFC differed in the healthy donors group. Such parameters also showed a significant variability with the number of cigarettes smoked and the years of smoking habit. Multivariate regression analyses showed a significant association between cytogenetic damage, ras p21 oncoproteins, and cancer. In conclusion, cytogenetic damage and ras p21 oncoproteins in this study appear to be biomarkers associated with cancer, but have not been proved causally, and confounding factors such as age, sex (gender), and smoking can have an impact on them.

Mutagenic analysis of 2,3-diaminophenazine and 2-amino-3-hydroxyphenazine in Salmonella strains expressing different levels of O-acetyltransferase with and without plant and mammalian activation.

2,3-Diaminophenazine (DAP) and 2-amino-3-hydroxyphenazine (AHP) are products generated from oxidative-type phenylenediamine hair dyes and are also present in pesticide formulations as contaminants. Earlier studies demonstrated that DAP and AHP were mutagenic in Salmonella typhimurium strains after mammalian microsomal activation. Plant systems can activate structurally similar arylamines. S. typhimurium strains have been developed that express elevated levels of acetyl-CoA: N-hydroxyarylamine O-acetyltransferase (OAT). O-acetyltransferase expression is necessary for the generation of the ultimate arylamine promutagen after plant activation. A number of arylamines including 2-aminofluorene, benzidine and 4-aminobiphenyl were activated by plant cells into mutagens in the OAT over-expressing S. typhimurium strain, YG1024. The objectives of this research were to examine the mutagenicity of DAP and AHP with mammalian or plant activation in Salmonella strains with different acetyltransferase activities. The hypothesis tested was whether and to what degree a metabolite of DAP or AHP could serve as a substrate for bacterial O-acetyltransferase and induce mutation in Salmonella. DAP and AHP without activation induced both frameshift and base pair substitution mutations in S. typhimurium strains that exhibited elevated levels of O-acetyltransferase activity. The mutagenicity of DAP and AHP were greatly enhanced with mammalian hepatic microsomal activation resulting in a preferential induction of frameshift mutations. With the hisD3052 allele as the gene target, S9-activated DAP induced frameshift mutations in YG1024 and TA98 as well as the OAT deficient strain TA98/1,8-DNP6. S9-activated AHP induced mutation only in the OAT over-expressing strain, YG1024. With the hisG46 allele, O-acetyltransferase activity was necessary for the metabolism of DAP and AHP to products that induce base pair substitution mutations. An intriguing finding of this work was the antimutagenic capacity of TX1MX, a plant cell-free activation mixture. TX1MX repressed the mutagenic activity of DAP and AHP at frameshift and base pair substitution mutation targets.

Biological monitoring of workers exposed to emissions from petroleum plants.

This paper presents some of the results from the Commission of the European Communities collaborative research program (contract number EV5V-CT92-0221), whose aim is to investigate the relationship between exposure to petroleum emissions, benzene, and induction of genetic damage in human cells. Twenty-four workers from petroleum plants in Poland and 35 unexposed controls were examined for cytogenetic effects and ras oncoprotein levels and their relationship to confounding factors (e.g., smoking habit, sex family cancer history, and seasonal influence). Preliminary data of chromosome aberrations (CA) and sister chromatid exchanges (SCE) showed differences among sampling subgroups. In this present study, the levels of ras p21 proteins were determined and further analyses of CA, SCE, high frequency cells (HFC), and proliferative rate index (PRI) have been undertaken. Results show that the exposed group has statistically significant increases in CA, and percent of aberrant cells. There were no differences between exposed and unexposed groups in SCE, HFC, PRI, or the levels of ras p21 proteins. Smoking was found to statistically significantly affect levels of CA, percent of aberrant cells, SCE, HFC, and ras proteins. Sister chromatid exchanges were also statistically significantly sex dependent (7.5 breaks/cells for females and 6.8 breaks/cell for males). There were no statistically significant differences for CA, percent aberrant cells, SCE, HFC, or ras p21 protein levels in subgroups characterized according to cancer cases reported in the immediate family. A seasonal variability was shown with statistically significant increases in various biomarkers in the winter. Unexposed groups also showed increases due to smoking and season. The nonsmoking group individuals also showed statistically significant increases in cytogenetic damage with exposure.

ras oncoproteins in human plasma from lung cancer patients and healthy controls.

In order to explore the significance of ras oncoproteins in plasma in the carcinogenic process, we have examined samples from 40 Polish human lung cancer patients prior to treatment. They were compared with 35 healthy donors and have been screened using a direct analysis of the plasma. Proteins were separated by gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting and detected by chemiluminescence, using monoclonal ras antibody as the primary antibody. Elevated increases in ras oncoproteins were determined where an increase was considered to be greater than 2 standard deviations above the mean negative control values. The results showed that in 45% of cancer patients ras oncoprotein levels were statistically significantly increased (P < 0.001, pooled two-sample t-test untransformed, and non-parametric Mann-Whitney test) in the plasma by comparison with 6% in the controls. This would suggest that an increase in ras oncoproteins in plasma could be a possible prognostic marker or biomarker for lung cancer.

Tradescantia stamen hair mutation bioassay.

The Tradescantia stamen hair mutation (Trad-SH) assay (clone 4430) was evaluated for its efficiency and reliability as a screen for mutagens in an IPCS collaborative study on plant systems. Four coded chemicals, i.e. azidoglycerol (AG, 3-azido-1,2-propanediol), N-methyl-N-nitrosourea (MNU), sodium azide (NaN3) and maleic hydrazide (MH) were distributed by the Radian Corporation to the five laboratories in five different countries for testing mutagenicity. Pink mutations were scored between the 7th and 14th day according to a standard protocol. Test results from the five individual laboratories were analyzed and compared after decoding. One out of the two laboratories that conducted tests on AG demonstrated that AG is a mutagen with genetically effective doses ranging from 50 to 100 micrograms/ml. MH yielded positive responses in all laboratories but no linear dose-response pattern was observed. The effective dose range for MH was between 1 and 45 micrograms/ml. The mutagenicity of MNU was reported by five laboratories in the dose range between 10 and 80 micrograms/ml. NaN3, which exhibited a relatively high degree of toxicity, elicited a positive mutagenic response in three of the five laboratories in which it was tested. As with MNU the effective dose for NaN3 ranged between 3 and 80 micrograms/ml. The results from the current study substantiate the Trad-SH assay as a reliable system for screening chemicals for their potential mutagenic effects. Although the study was carried out exclusively under laboratory conditions, a survey of the current literature would indicate that the Trad-SH assay could be an effective in situ monitor of gaseous, liquid, and radioactive pollutants as well.

Tradescantia stamen-hair mutation bioassay on the mutagenicity of radioisotope-contaminated air following the Chernobyl nuclear accident and one year later.

This paper presents results of the research on the mutagenic effect of ambient air in the Cracow area. Initial studies were conducted in May 1986, following the Chernobyl accident. Other studies were performed at various sites within the Cracow area in the Spring of 1987. Counts were made of stunted hairs and pink cells in the stamen hairs of Tradescantia clone 4430. Mutations scored from the 11th day after the beginning of exposure were used as a measure of the mutagenic effect. The mean mutation frequencies measured in 1986 and 1987 were 0.43 and 0.21 per 100 hairs respectively. The time-dependent development of mutation frequencies observed after the Chernobyl accident showed a correlation with the time-dependent development of total radioactivities measured in the air at that time. The results obtained in 1987 showed on average a significant decrease of ambient air mutagenicity. Still, the variation of mutation rates observed during the investigated period at different sites in the Cracow area was rather high (0.09-0.38 mut/100 hairs). Only the highest frequencies observed in the Spring of 1987 were comparable to the level detected after the Chernobyl accident.

Interleukin-1 modification of the effects of cyclophosphamide and fractionated irradiation.

Studies were performed to determine whether recombinant human interleukin-1 (IL-1) modifies the tumor cytotoxicity of cyclophosphamide (CY) combined with fractionated X-irradiation. RIF-1 tumors were implanted intradermally in C3H/Km mice and therapeutic effect was evaluated by the regrowth delay method, that is, the time for treated tumors to grow to 3 times their volume at the start of treatment relative to that for untreated tumors. A single intraperitoneal treatment of 15 micrograms/kg IL-1 given 24 hr after 100 or 200 mg/kg CY and immediately before the first of 5 daily fractionated treatments of 1-4 Gy increased tumor growth delay beyond that produced by CY and irradiation without the IL-1. However, the IL-1 given with either CY or fractionated irradiation did not extend the time for tumor regrowth beyond that produced by the agents themselves. Thus, while CY and fractionated irradiation together produce a greater than additive effect, IL-1 seems to extend this phenomenon. From these findings, it appears that IL-1 enhances the cytotoxic effects of CY and X ray against tumors, an effect that would have considerable practical significance in the light of the protective effects shown elsewhere for the same lymphokine on normal tissues.

[Mutagenicity of environmental air in Cracow monitored by the Tradescantia stamen hair system]. / Mutagennosc otaczajacego powietrza w krakowie monitorowana w ukladzie wlosków precików u Tradescantia.

Three times since 1983, groups of plants of Tradescantia clone 4430 have been exposed to ambient air on various sites of the Cracow area. The highest value of mutation frequency was noted in May 1986 after the Chernobyl accident. A slightly lower level of mutation frequency but comparable in value was riched in 1983 in vicinity to a pharmaceutical factory in result of chemical mutagen emissions. In various periods of 1987 temporary differences between the levels of mutations were observed on various sites in Cracow. There was also noted a significant decrease in the mean mutation level in comparison with the levels observed in 1983 and 1986.