[Features of coarse calico damage by hollow-point bullets of ammunitions to a 12-gauge fire smoothbore weapon (12×70) under the conditions of remote shooting distance]. / Osobennosti povrezhdeniya byazevoi tkani ekspansivnymi pulyami patronov k ognestrel'nomu gladkostvol'nomu oruzhiyu 12-go kalibra (12×70) v usloviyakh neblizkoi distantsii vystrela.

The article presents the experimental study results of damaged clothes imitators' (coarse calico) features in consequence of shot by ammunitions with hollow-point bullet from a 12-gauge fire smoothbore weapon (12×70). The generation mechanism of coarse calico damage during wound of underlying biological human body's imitator by bullet and the factors influencing on mentioned process have been clarified using high-speed video recording.

[Criteria for the determination of the distance of a gunshot from limited-range firearms based on the morphological characteristics of the wound and the results of inductively coupled plasma mass spectrometry].

We have developed the criteria allowing to determine the distance of a gunshot from limited-range firearms (an IZh-79-9TGM pistol with the elastic bullet cartridges) based on the morphological characteristics of the wound and the results of inductively coupled plasma mass spectrometry. The method has been developed for the quantitative determination of barium, lead, and antimony in the targets depending on the gunshot distance.

Supply voltage control for guaranteed performance of compact terahertz vacuum electron devices.

The results of the concept development of the universal high-voltage power supply with the output parameters providing the reliable operation of compact THz vacuum electron devices have been presented and discussed. The low-level of high-voltage ripples less than 10 ppm at 6 kV, 250 mA was obtained with the help of the designed high-precision and fast-response stabilization scheme. Real-time stabilization of the output parameters of vacuum electron devices was realized by using the multiloop proportional-integral-differential feedback control and was tested with the continuous-wave clinotron tubes in millimeter range. The developed high-voltage power supply offers the high-voltage modulation mode that allows applying the THz tubes with electronic frequency tuning for frequency-modulated continuous wave radar applications.

Modulation of repair of O6-methylguanine in parenchymal and nonparenchymal liver cells of rats treated with dimethylnitrosamine.

Previous studies have shown that chronic treatment of rats with dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) results in increased repair of O6-methylguanine (O6-mGua) in liver DNA. The experiments reported here try to determine if this increased repair is confined to one or more cell populations of the liver. Liver cells [parenchymal (PC) and nonparenchymal (NPC)] were separated by elutriation centrifugation at various times after the last administration of DMN. The in vivo alkylation studies show that at any time after a dose of [14C]DMN (2 mg/kg) the level of O6-mGua in PC cells of DMN pretreated rats was much lower than in the same cell population from control rats receiving only a single dose of DMN. In contrast, the pretreatment schedule resulted in no change in the levels of this DNA adduct in NPC cells. These results were confirmed by the determination of the levels of O6-methyldeoxyguanosine by radioimmunoassay in DNA from PC or NPC cells of rats similarly either pretreated for 3 weeks with DMN or receiving a single dose of DMN (2 mg/kg). The in vitro measurements of O6-mGua DNA alkyltransferase activity, using alkylated DNA as substrate, also show a higher activity of this repair enzyme in PC cells. The DMN pretreatment resulted in a 25-fold difference in O6-mGua DNA alkyltransferase activity between the two cell populations of the liver.

5-Bromodeoxyuridine-induced carcinogenesis and its modification by persistent estrus syndrome, unilateral nephrectomy, and X-irradiation in rats.

We showed earlier that 5-bromodeoxyuridine (BrdUrd), which can substitute for thymidine during DNA synthesis, inducing transition mutations, is incorporated into DNA of various tissues when administered to newborn rats and is not subjected to repair processes. The main purpose of the present experiment is to verify if a direct perturbation of DNA would be sufficient to initiate carcinogenesis. Rats aged 1, 3, 7, and 21 days were given BrdUrd s.c. at a dose of 3.2 mg/animal. At 2 months some of the females were subjected to treatment known to induce persistent estrus; at 1 month a group of males underwent removal of one kidney, and groups of males and females were exposed to a single total-body X-irradiation at a dose of 1.5 Gy (150 rads) per rat. In females, treatment with BrdUrd induced tumors of the ovaries, polyps in the uterus, and tumors of the soft tissues, nervous system, forestomach, glandular stomach, and salivary gland; no such tumor occurred in control females. Induction of persistent estrus increased the incidences of ovarian tumors and of malignant tumors of the uterus. Treatment with BrdUrd also increased the carcinogenic effect of X-rays on the mammary gland. In males, BrdUrd induced tumors of the testis (seminomas) and adenomas of the thyroid gland; solitary tumors of the kidney, nervous system, soft tissues, and bladder were also found. Unilateral nephrectomy reduced the incidences of tumors in the testis and pituitary gland, whereas subsequent treatment with X-rays did not alter the incidences of tumors induced by BrdUrd. These studies demonstrated for the first time that a nucleoside analogue, BrdUrd, has carcinogenic potential. Possible molecular mechanisms for its carcinogenicity and for the effects of the promoting factors are discussed.

Carcinogenicity of single doses of N-nitroso-N-methylurea and N-nitroso-N-ethylurea in Syrian golden hamsters and the persistence of alkylated purines in the DNA of various tissues.

The carcinogenicity of N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) has been determined in adult male Syrian golden hamsters following a single i.p. injection or two-thirds of the acute 50% lethal dose, or 30 and 60 mg/kg, respectively. The principal site of action of these agents was the forestomach, squamous cell papillomas of this organ developing in 53 and 61% of the animals receiving the higher doses of NMU and N-nitroso-N-ethylurea, respectively. NMU also induced a low incidence of liver tumors (17%). Very few tumors were seen at other sites. The formation and removal of alkylated purines in DNA was measured in various tissues up to 50 hr after administration of [14C]NMU. Methylation products were detected in all tissues examined, the level in liver being somewhat higher than in other tissues. The removal of 7-methylguanine and 3-methyladenine from DNA occurred at approximately similar rates in all tissues examined, indicating no substantial differences in N-glycosylase activities. Removal of the promutagenic DNA lesion O6-methylguanine varied considerably from tissue to tissue; very little occurred in brain or kidney, while up to 36 and 32% were lost from DNA of intestine and testes, respectively. In the liver, there were relatively small changes in O6-methylguanine levels up to 24 hr; but by 50 hr, 38% had been removed. The persistence of O6-methylguanine relative to 7-methylguanine was highest in the DNA of the brain and intestine and lowest in that of the liver. These results indicate that in this experimental system, the formation and persistence of O6-methylguanine in DNA is insufficient alone to account for the organotropic effect of NMU.

High benzo[a]pyrene diol-epoxide DNA adduct levels in lung and blood cells from individuals with combined CYP1A1 MspI/Msp-GSTM1*0/*0 genotypes.

Levels of anti-benzo[a]pyrene diol-epoxide DNA adducts were analysed by high-pressure liquid chromatography/fluorimetric detection in non-tumorous lung tissues from 20 lung cancer patients and in white blood cells from 20 polycyclic aromatic hydrocarbon exposed coke oven workers. All were current tobacco smokers. CYP1A1 mutations (MspI at 6235 nt, Ile-Val462) and GSTM1 deletion polymorphisms in each individual were analysed in genomic DNA by PCR/restriction fragment length polymorphism. Independently of the CYP1A1 genotype (1) all 23 samples in the two groups with non-detectable adducts (< 0.2 per 10(8) nt) were of GSTM1 active genotype; (2) the 17 samples with detectable adducts (> or = 0.2 per 10(8) nt) in the two groups were GSTM1*0/*0. The difference in adduct levels between GSTM1*0/*0 and GSTM1 active genotype was highly significant (p < 0.00005). Among GSTM1-deficient individuals (n = 17), a subgroup of 14 individuals with CYP1A1*1/*1 (wild-type, n = 7) or heterozygous genotype (*1/*2A or *1/*2B, n = 7) showed low levels of BPDE DNA-adducts (range: 0.2-1.3 per 10(8) nt). (3) Three individuals with the rare combination CYP1A1*2A/*2A or *2A/*B and GSTM1*0/*0 showed significantly higher adduct levels (median: 17.4 adducts/10(8) nt, range 1.9-44; p = 0.017). Therefore, combination of homozygous mutated CYP1A1 and GSTM1*0/*0 genotypes lead, at a similar or even lower smoking dose, to a stronger increase of anti-benzo[a]pyrene diol-epoxide DNA adduct levels than found in individuals with CYP1A1 and GSTM1 wild-type. These data provide a mechanistic understanding of epidemiological studies that correlated these 'at risk' genotypes with increased smoking-related lung cancers.

Repair of DNA alkylation adducts in mammalian cells.

Carcinogenic alkylating agents, including nitrosamines, are able to alkylate DNA at various sites. This review presents evidence of the high degree of specificity in the type of DNA damage induced by various N-nitroso compounds and in the DNA repair processes among tissues or cells of different species. The O6-alkylguanine DNA alkyltransferase activity in various human and rodent tissues is discussed as well as the detection of O6-methylguanine in human DNA, using monoclonal antibodies and radioimmunoassay. The relevance of these findings to the mechanisms of cancer induction by nitrosamines is discussed.

Individual levels of activity of O6-alkylguanine-DNA alkyltransferase in monkey gastric mucosa during chronic exposure to a gastrocarcinogen N-ethyl-N'-nitro-N-nitrosoguanidine.

The activity of a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), was studied in gastric mucosa of 15 Macaca fascicularis monkeys before and during chronic oral exposure to the ethylating carcinogen N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in order to investigate possible causes of inter-individual differences in susceptibility to its gastrocarcinogenic effect. A wide range of AGT activity (307-1903 fmol/mg protein, mean 695) was found before treatment and it decreased during the first year of exposure (means 627, 479 and 452 fmol/mg protein respectively at 6, 12 and 18 months after the beginning of the experiment). The carcinogenesis study is under way and to date four monkeys with low initial AGT level in gastric mucosa died of gastric cancer. The relevance of AGT level measurement for prediction of individual susceptibility to ENNG is discussed.

Methylation of thymine and uracil with free methyl cations formed due to beta-decay of tritiated methane: possible implication in mutagenesis and carcinogenesis.

Exposure of solid thymine and uracil at room temperature to free methyl cations, produced due to beta-decay of tritiated methane, resulted in formation of their 1-, O2-, 3-, O4-, and 6-methyl derivatives. In addition, uracil formed a 5-methyl derivative (thymine); tritium-containing thymine and uracil were also detected. Both thymine and uracil formed predominantly unidentified products which resulted presumably from their oligomerization. Incubation at -195 degrees C did not markedly change the pattern of reaction products. Aqueous-ammonia solutions of these pyrimidines formed methylated derivatives and considerable amounts of methanol and tritiated water. The possible implication of these reactions in mutagenic and carcinogenic effects of tritium-substituted hydrocarbons is discussed.

Dependence of 1,2-dimethylhydrazine metabolism on its treatment schedule.

The content of cytochromes P-450 and b5 in rat liver microsomes, as well as the extent of labeling of nucleic acids and proteins of the liver and kidneys and of mucosa from different intestinal segments, was studied in rats injected daily or once a week subcutaneously with similar total doses of 1,2-dimethyl-hydrazine (SDMH) and in untreated rats. Daily SDMH administrations led to a decrease in cytochrome P-450 activity. Pretreatment of rats with unlabelled SDMH resulted in decreased labeling of DNA, RNA, proteins, and acid-soluble fractions after [3H]SDMH injection. A more pronounced effect was found after the daily treatment.

Persistence of carcinogenic effect in intact progeny of mice treated transplacentally with 7,12-dimethylbenz[a]anthracene.

Pregnant SHR mice were treated once with 7,12-dimethylbenz[a]anthracene (DMBA) on days 17-19 of gestation. F1 and F2 descendants of these mice received multiple skin applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week for 24 weeks beginning at 12 weeks of age, or applications of solvent alone. The increase in the frequency of skin tumours in F1 and F2 descendants was reported elsewhere. In addition, we report here an increase in overall numbers of tumor-bearing animals, independently of TPA treatment both in F1 and F2 groups compared to respective control groups. Separate statistical analyses were performed for lung tumours, mammary gland tumours, leukaemias and lymphomas. In both generations of descendants of DMBA-treated mothers lung tumour incidence was considerably increased and differed significantly (maximal P-value = 0.003) from control values. Local applications of TPA resulting in strong skin tumour promoting effect described in our previous paper (Napalkov et al., Carcinogenesis, 8(3) (1987) 381) did not produce any significant change in the rates of other types of tumours. The results of the present study provide additional evidence in support of the hypothesis on possibility of hereditary transmission of carcinogenic action of certain chemical compounds.

Individual values of excretion of benzo[a]pyrene metabolites and susceptibility to its carcinogenic effect in rats.

In white outbred LIO rats exposed to multiple intraperitoneal (i.p.) doses (10 mg/kg) of benzo[a]pyrene (BP) in the form of a water-lipid emulsion, individual peculiarities of the excretion of its metabolites, BP-7,8-diol and 3-hydroxy-BP (3-OH-BP) in urine and feces were detected and compared with the carcinogenic effect. Parameters of BP metabolite excretion differed from those found in our previous experiments with rats exposed to single high i.p. doses of BP (100 and 200 mg/kg), dissolved in sunflower oil [11,12]. In comparison with our previous observation, in the present study, the carcinogenic effect was considerably weaker (5/22 versus 10/19). The rats that developed tumours of internal tissues (four peritoneal malignant histiocytomas and one lung lymphosarcoma), excreted higher quantities of BP-7,8-diol in the urine than other rats. The possible implication of monitoring excretion of BP metabolites for predicting individual susceptibility to its carcinogenic effect is discussed.

Biomarkers for individual susceptibility to carcinogenic agents: excretion and carcinogenic risk of benzo[a]pyrene metabolites.

In rats exposed to a single intraperitoneal dose of 200 mg/kg of the environmental carcinogen benzo[a]pyrene (BP) in sunflower oil, significant individual variations in excretion of the BP activation (BP-7,8-diol) and deactivation (3-OH-BP) derivatives were found. Most rats developed peritoneal sarcomas. Only the levels of BP-7,8-diol excreted in the urine correlated directly with the latency of tumor formation. After a similar exposure to a dose of 100 mg/kg BP, Macaca fascicularis monkeys excreted smaller quantities than rats of both metabolites. After rats were given 10 intraperitoneal injections each of 10 mg/kg of BP in a water-lipid emulsion, the excreted levels of both metabolites after the first, fifth, and tenth injection were lower than those of the rats that received 200 mg/kg. BP metabolites were also detected in the urine of lung cancer patients who were heavy smokers. The applicability of monitoring the excretion of the BP metabolites to predicting individual cancer risk is discussed.

Incorporation of 5-bromodeoxyuridine into DNA in newborn rat tissues.

The incorporation of bromodeoxyuridine (BUdR) into newborn rat tissue DNA has been determined after i.p. injection of 5-bromo-2'-deoxy-[6-3H]uridine. Incorporation of the unchanged nucleoside was shown by hydrolysis and ion exchange chromatography of extracted DNA. In all tissues examined, more than 90% of the radioactivity incorporated was in the form of bromodeoxyuridine.

Alkylated purines in the DNA of various rat tissues after administration of 1,2-dimethylhydrazine.

[1,2-3H] Dimethylhydrazine (1,2-DMH) (300 mg/kg; 4 mCi/kg) was injected s.c. to BD-VI rats and the degree of DNA alkylation was measured in various tissues 3 h after the administration. The O6-methylguanine/7-methylguanine ratio was approx. 4 times higher in the colon's DNA (0.0565), the principal target organ of this carcinogen, than in the liver's DNA (0.0136). These findings are briefly discussed in relation to the organ specificity of this carcinogen.

Incorporation and persistence of 5-bromodeoxyuridine in newborn rat tissue DNA.

One-day-old BDVI rats were given a mixture 5-[3H]bromodeoxyuridine (BrUdR) and [14C]thymidine (each at 20 mg/kg; 12.8 and 3.53 mCi/mmol, respectively) by intraperitoneal injection. DNA was isolated by a phenol procedure from various pooled tissues up to 21 days later and the levels of BrUdR and thymidine incorporation were determined after formic acid hydrolysis and Dowex-50 chromatography. Incorporation increased to a maximum at 12 h then decreased, the decrease of both products occurring in parallel in all tissues examined but differing in kinetics from tissue to tissue. After 12 h, the relative amounts of 3H and 14C showed no consistent or marked decreases and this suggests that BrUdR is not actively removed from DNA by a repair process under these experimental conditions. This was also the case after a much lower dose of these agents (9 micrograms/kg [3H]BrUdR 22.6 Ci/mmol; 1.3 mg/kg [14C]thymidine 53 mCi/mmol) when the 3H/14C ratios in DNA from various tissues were increased relative to the higher dose and showed only slight differences between 15 h and 21 days after administration.

In vivo alkylation of foetal, maternal and normal rat tissue nucleic acids by 3-methyl-1-phenyltriazene.

The carcinogen 3-methyl-1-phenyltriazene (MPT) was administered subcutaneously to normal or pregnant BD VI rats and DNA and RNA were isolated from various tissues after 8 h or 15 h, respectively. Sephadex G-10 chromatography of DNA hydrolysates showed the presence of 7-methylguanine in all tissues examined including that of the brain, one of the target organs for tumour induction. The amounts of the minor product, O6-methylguanine, were characteristic of an SN1 reaction mechanism. Dowex-50 chromatography of RNA hydrolysates showed the presence of 7-methylguanine and of the minor product, 3-methylcytosine. The relative amounts, both of the methylated bases in the individual nucleic acids and of 7-methylguanine in DNA and RNA, were similar to those found previously after administration of 3,3-dimethyl-1-phenyltriazene (DMPT). This suggests the involvment of a common alkylating intermediate. De novo incorporation of radioactivity into purine bases was detected in both DNA and RNA although the levels were not related to the amounts of methylation. The results show that MPT is sufficiently stable to alkylate nucleic acids in vivo and are consistent with the hypothesis that this reaction is a prerequisite for tumour induction. Futhermore, they support the proposal that MPT is the active intermediate in the induction of tumours by DMPT.

[Characteristics of the carcinogenic action of methyl(acetoxymethyl)nitrosamine and DNA repair in rats of different ages]. / Osobennosti kantserogennogo deistviia metil(atsetoksimetil)nitrozamina i reparatsii DNK u krys raznogo vozrasta.

A pattern of DNA methylation and carcinogenesis has been studied in young (3 month-old) and old (14 month-old) female rats following a single intravenous injection (13 mg/kg) of methyl(acetoxymethyl)nitrosamine (DMN-OAc). The incidence of various tumours as well as the incidence of tumours in some peculiar sites were found to be similar in young and old DMN-OAc-treated rats. The life time of old rats was less than that in young animals; the average period of tumour detection was also shorter in old rats. In both young and old animals the highest concentrations of methylated purines were found in lung and kidney DNA. However, the level of DNA methylation in old rats was higher than in corresponding tissues of young animals. Efficiency of O6-meG repair in methylated template DNA was found to be the highest in liver extracts of 1- and 12-month-old rats. Further, by the age of 2 years, the activity of O6-meGT decreased. The findings suggest that different age periods could be characterized by different efficiency of DNA alkylation, synthesis and repair.

[The carcinogenic effect of 5-bromodeoxyuridine and its amplification by x-rays in rats]. / Kantserogennyi éffekt 5-bromodezoksiuridina i ego usilenie rentgenovskim oblucheniem u krys.

5-bromodeoxyuridine (BUdR) injected to rats in the neonatal period is shown to produce a pronounced carcinogenic effect which brings about the appearance of various benign and malignant tumours. Exposure of females to X-ray total-body irradiation (1.5 Gy) was followed by intensification of the carcinogenic effect of BUdR. Assuming that this pyrimidine analog reacts solely with DNA substituting thymidine during DNA synthesis and induces point mutations due to tautomerization, the data obtained demonstrate the possibility of tumour induction by a selective DNA perturbation.