Male mice Sfis:Pzh were exposed to X-rays, cyclophosphamide or combination of both agents. Each of agent was given in low (0.25 Gy, 25 mg/kg bw CP) or high (1.00 Gy, 100 mg/kg bw CP) doses. Germ cells were exposed to agents as spermatogonia. After 35 days sperm abnormalities test was performed. Exposure to one of agents only, did not enhance statistically significant frequency of morphologically abnormal spermatozoa. Combined treatment of spermatogonia to both agents in low as well in high doses induce clear biological effects, but only combination of high doses (1.00 Gy + 100 mg/kg bw CP) induce statistically significant effect. Results obtained in this study confirmed, that ability of different agents to induce sperm-shape abnormalities is related to its ability to induce mutations in germ cells.

People can be exposed to 1,3-butadiene in work place (rubber industry) as well as in natural environment (car exhausts fumes, cigarette smoke). Butadien on its own is not genotoxic, but is metabolized to mutagenic and carcinogenic epoxydes, 1,2,3,4-diepoxybutane and 3,4-epoxybutene in the organism of mammals and human. 1,3-butadiene has been shown to be a potent carcinogen in animals and human. Laboratory investigations showed also toxic and mutagenic abilities of butadiene and its metabolities. Interspecies differences in sensitivity to butadiene are caused by differences in metabolic transformations of butadiene in different species.

The induction of micronuclei in polychromatic erythrocytes of bone marrow of Pzh:SWISS mice after combined treatment with X-rays and cyclophosphamide (CP) or X-rays and mitomycin C (MMC) were investigated. Combinations of high (1.00 Gy + 100 mg/kg bw CP and 1. 00 Gy + 5.25 mg/kg bw MMC) and low (0.25 Gy + 25 mg/kg bw CP and 0. 25 Gy + 1.75 mg/kg bw MMC) doses were used. Both chemicals enhanced the mutagenic effects caused by irradiation. After combined treatment with high doses of X-rays + CP and X-rays + MMC at different sample times increases in frequency of micronuclei were observed. Mutagenic effects were found also after treatment with two low doses, when irradiation alone produced no effects. The effects of combined treatments are generally similar to the additive effect of the single treatments.

The induction of dominant lethal effects and sperm abnormalities in Pzh:Swiss male mice after treatments with X-rays and mitomycin C (MMC) was investigated. Combinations of high (1.00 Gy + 5.25 mg/kg bw MMC) and low (0.25 Gy + 1.75 mg/kg bw MMC) doses of both agents were used. Exposure to high doses of X-rays + MMC induced an increased rate of dominant lethal mutations in spermatogonia and late spermatocytes. Combined treatment with low doses of X-rays and MMC was not mutagenic in any stage of spermatogenesis. MMC increased the frequency of abnormal spermatozoa after exposure alone and in combination with X-rays. Treatment with two high doses (1.00 Gy + 5.25 mg/kg bw MMC) induced 58.4% abnormal spermatozoa. After combined exposure to low doses of both agents 35.7% spermatozoa with malformations were observed.

OBJECTIVE Comparison of the mortality of male members of the Polish Olympic teams with the general Polish male population for the period 1981-1998 and for two sub-periods 1981-1991 and 1992-1998. METHODS Statistical approach based on the follow-up method. Comparison with the reference population (Polish males from urban areas) was made by means of the standardized mortality ratios (SMRs) and their 95% confidence intervals. The series test (Wald-Wolfowitz test) was applied to assess the mortality difference in 1981-1991 and 1992-1998. MAIN OBSERVATIONS A total number of 1,769 male members of the Polish Olympic teams were identified. Of those, 148 died before 1981 and 116 were excluded from the analysis because of incomplete data records. Finally analyzed cohort included 1,505 athletes of the age 14-99 years, who contributed 21,575.8 person-years of observation. 131 deaths were noted during the analyzed period. RESULTS Calculated SMR for the analyzed group of sportsmen was 0.420; 95% confidence interval: 0.351-0.498. All age-specific SMRs was lower than in general population. The athletes' mortality in 1992-1998 was significantly lower than in 1981-1991. CONCLUSION Polish participants in Olympic Games were proved to exhibit significantly lower mortality than general Polish male population throughout their life. The decrease in sportsmen mortality decrease in 1992-1998 was stronger than observed for the reference population.

The NATO Science Programme joining in the celebration of 50th Anniversary of Founding of the NATO by organisation of NATO Advanced Study Institute "Human Monitoring after Environmental and Occupational Exposure to Chemical and Physical Agents", which was held in Tekirova-Antalya (Turkey), September 23-October 3, 1999. The director of ASI was dr Diana Anderson from TNO-BIBRA (UK). The members of Scientific Organizing Committee were also dr R. Sram (Czech Republik), dr A. Karakaya (Turkey), Dr P. O'Neill (USA), dr R. Bos (Netherlands), dr M. Lotti (Italy). It was a high-level tutorial course for scientists at the post-doctoral level from NATO countries and from NATO Cooperation Partner countries. NATO-ASI attended about 100 scientists from about 30 countries. There were 40 lectures, 20 oral presentations and 43 posters presented, 19 authors of posters were invited to additional short oral presentations. Subject of course concerned undesirable effects of chemical and physical agents on human health. The aim of NATO-Advanced Study Institute was the meeting of scientists working in different fields of science to present and discuss the knowledge and recent developments in the field of human monitoring. The majority of lectures concerned about biomonitoring of people exposed to genotoxic agents at work place and environment. Dr A. Autio (Switzerland) presented definitions of different kinds of bimarkers proposed by the Committee on Biological Markers in Environmental Health of USA Academy of Science/National Research Council. Dr D. Anderson (UK) introduced history of biomonitoring. The main lecturers on this topic were dr W. Au (USA), dr R. Sram (Czech Republik), dr M. Lotti (Italy), dr J. Timbell (USA), Dr E. Moustacchi (France). The following group of lectures presented by dr D. Anderson (UK), dr A. Wyrobek (USA), dr J. Bonde (Dennmark), dr H. Norppa (Finland) was regarded to male-mediated mutagenic effect in offspring induced by genotoxic physical and chemical agents. This part of course was the most interesting to the author of this report. She has presented the poster "Male-mediated F1 effects in mice subchronic exposed to low doses of X-rays". The author of this report found NATO-ASI as very fruitful initiative for scientific view-exchange between scientists from NATO countries and for NATO Cooperation Partner countries.

People are widely exposed during their lifetime to many biological, chemical, and physical agents in the environment and at work. In this paper the effects of combined exposures of nonmutagenic doses of X-rays and anticancer agents (cyclophosphamide, mitomycin C, and vinblastine) have been investigated on the induction of micronuclei in the bone marrow of laboratory mice. The combination of X-rays and anticancer drugs enhanced the frequency of micronuclei in some cases. The strongest effects were found after the combination of X-rays and cyclophosphamide at 24 h and 72 h. The combined treatment of X-rays and mitomycin C enhanced the mutagenic effect at 72 h. The combination of X-rays + vinblastine slightly potentiated the mutagenic effect at 24 h and 48 h.

The use of food additives in various products is growing up. It has attracted the attention towards the possible correlation between the mutagenic potential of food additives and various human diseases. This work evaluated the protective role of selenium and vitamins A, C and E (selenium ACE)(1) against the genotoxic effects induced by a synthetic food additive, sunset yellow, in mice. Six groups were studied including two control groups (negative and positive control), two groups are given single dose of sunset yellow (either 0.325, 0.65 or 1.3mg/kg body weight(2) alone or with selenium ACE) and two groups are given sunset yellow daily for 1, 2 or 3 weeks (0.325mg/kg b.wt./day alone or with selenium ACE), respectively. The study examined the induction of sister chromatid exchanges (SCE's)(3) in bone-marrow cells, chromosomal aberration in somatic (bone-marrow) and germ cells (spermatocytes) after single and repeated oral treatment, and the induction of morphological sperm abnormalities. The results showed that sunset yellow had genotoxic effects as indicated by increased frequency of SCE's, by chromosomal aberrations in both somatic and germ cells, and by increased morphological sperm abnormalities and DNA fragmentation. The results also indicated that the oral administration of selenium ACE significantly reduced the genotoxic effects of sunset yellow, a result that may support the use of antioxidants as chemopreventive agents in many applications.

This study was designed to investigate the effects of 2 weeks of exposure of male mice to bisphenol A (BPA) alone or in a combination with X-rays on the sperm count and quality as well as induction of DNA strand breaks in somatic and germ cells. Pzh:SFIS male mice were exposed to X-rays (0.05 and 0.10 Gy) or BPA (5, 10, 20, and 40 mg/kg) or to a combination of both (0.05 Gy + 5 mg/kg body weight of BPA and 0.10 Gy + 10 mg/kg of BPA). Both X-rays and BPA administered alone decreased sperm count and quality. X-rays induced DNA strand breaks in spleen cells, whereas BPA induced DNA strand breaks in lymphocytes and in cells from spleen, kidneys, and lung and in germ cells. After combined exposure to both agents, sperm count and quality were similar as after exposure to each agent alone and significantly reduced, compared to control. Levels of DNA damage in somatic and germ cells after combined exposure to lower, as well as higher, doses were significantly reduced, compared to the effects of BPA alone. Results confirmed the mutagenic ability of BPA. Combined exposure to X-rays and BPA leads to the prevention of DNA damage in somatic and germ cells of mice.

Tryptizol(®)[amitriptyline HCl (AT); El-Kahira Pharmacological and Chemical Co., Cairo, Egypt], a widely used antidepressant drug in Egypt, was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. Three doses were tested (low, medium, and high); they were chosen according to the drug manufacturer. The low-dose group received orally 1 mg/kg body weight (b.w.) daily for a total period of 1 month; the medium-dose group received 1 mg/kg b.w. daily for 15 days and 2 mg/kg b.w. daily for another 15 days; and the high-dose group received 1 mg/kg b.w. daily for 10 days, then 2 mg/kg b.w. daily for another 10 days and, finally, 4 mg/kg b.w. daily for 10 more days. The results showed that AT treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, AT significantly reduced both the mitotic index and meiotic activity after the different treatments used. AT was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased with the 3 doses tested. In general, results of chromosome abnormalities in both somatic and germ cells as well as sperm morphology and count showed that the effect of AT was dose dependent. The results of the current study showed that AT is a genotoxic agent for both somatic and germ cells and should be taken under special precautions and medical supervision.

In a previous study we have demonstrated that cold aqueous extract of Baccharis articulata (Ba-CAE) induced the death of human peripheral blood mononuclear cells (PBMCs) and exerted low mutagenic effects on mice at 6h after administration. The aim of this work was to investigate whether the PBMCs death induced by Ba-CAE is due to apoptosis, and whether this extract exerts mutagenic effects on mice at 24 and 48h after administration. In addition, Ba-CAE was chemically characterized. PBMCs from healthy volunteers were exposed to extract (10, 20, 40, 80, 160, 320, 640 and 1280μg/mL) for 18-24h. Cell viability was determined by staining of trypan blue dye exclusion method. Apoptosis was determined by Hoechst 33258 staining, TUNEL, and DNA fragmentation analysis by agarose gel electrophoresis. BALB/c mice were injected with extract (1800, 900 and 450mg/kg) and sacrificed at 24 and 48h postinjection. Bone marrow samples were used to assess chromosome mutations by the micronucleus test. The extract induced PBMCs death by apoptosis and increased the frequency of micronuclei in bone marrow. The phytochemical study of Ba-CAE showed the presence of flavones as luteolin and acacetin, caffeoylquinic acids as chlorogenic acid, and tannins.

Nonylphenol (NP) is an environmental chemical with estrogenic activity. Exposure of the general population to radiation and NP is, very often, unavoidable because of the presence of both agents in the environment of human life and work. The aim of the study was to investigate the effect of subchronic 8-week exposure to NP alone or in combination with X-rays on sperm quantity and quality and on the possibility of the transmission of mutations induced in germ cells to the next generation. Eight-week exposure to NP and X-ray/NP combination diminished sperm count and increased the percent of abnormal spermatozoa, as well as having increased DNA damage in gametes. Some of those effects remained up to 8 weeks after the end of exposure. The exposure of males to 50 mg/kg body weight (b.w.) of NP and to 0.05 Gy + 25 mg/kg b.w. NP daily significantly decreased the percent of pregnant females. The fertilization ability of male mice was not diminished. Combined exposure to low doses of both agents significantly increased the mean number of dead implantations per pregnant female and the percentage of skeletal malformations. Results showed that mutations induced in germ cells by subchronic exposure to NP and to combined X-ray/NP exposure may be transmitted to the F1 generation via sperm.

Natamycin [corrected] is used as preservative in foods. The genotoxic effects of the food preservative natamycin [corrected] were evaluated using chromosome aberrations and micronucleus test in bone marrow cells and sperm head abnormality assays in mice. Blood samples were taken from mice and levels of total testosterone in serum were also determined. Natamycin [corrected] was intraperitoneally (ip) injected at 200, 400 and 800 mg/kg. Natamycin [corrected] did not induce chromosome aberrations but significantly increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm head abnormalities at all concentrations and treatment periods. It also decreased MI at all concentrations for 6, 12 and 24h treatment periods. Natamycin [corrected] decreased PCE/NCE ratio at all concentrations for 48h in female mice, for 24 and 48h treatment periods in male mice. At the 800 mg/kg concentration, natamycin [corrected] decreased PCE/NCE ratio for 24 and 72h in female mice. A dose dependent increase was observed in the percentage of sperm head abnormalities. The levels of serum testosterone decreased dose-dependently. The obtained results indicate that natamycin [corrected] is not clastogenic, but it is aneugenic in mice bone marrow and it is a potential germ cell mutagen in sperm cells.

PURPOSE The aim of this study was to evaluate the potential genotoxicity induced by chronic oral exposure to depleted uranium (DU). MATERIALS AND METHODS Weanling Wistar rats (F(0)), 50/sex/group, were exposed to DU in food at doses of 0, 4, or 40 mg kg(-1)day(-1) for four months. They were subsequently mated, resulting in the birth of F(1) rats. Fifty F(l) weanlings/sex/group were exposed for four months to the same dose levels as their parents. After four months, the uranium content in the tissues, the potential damage to the genetic material, and pathomorphological changes of the testicles were observed in both F(0) and F(1) rats. The genotoxicity of DU was evaluated by the following methods: sperm abnormality assessment, the bone-marrow micronucleus test, and the comet assay. RESULTS Uranium content in F(1) rats was significantly higher than that in F(0) rats in both the kidney and ovary (p < 0.05). The sperm abnormality rate, marrow cell micronuclei rate, comet tail length, and tailed cell percentage increased in each treatment group in each generation compared with the control group (p < 0.05). When comparing F(1) with F(0) rats, significant differences were detected for most of the indicators, with F(1) rats always exhibiting more damage (p < 0.05). With regard to pathomorphological changes in the testicles, the sperm displayed atypical changes, including thickening of the anachromasis nucleolus, which seemed to be more severe in F(1) rats. CONCLUSION Genotoxicity may be induced in rats after chronic oral exposure to a low dose of DU.

The aim of the research was to investigate the level of micronuclei induction in reticulocytes and polychromatic erythrocytes of mice following subchronic exposure to X-rays, nonylphenol (NP) or to a combination of both. Male mice Pzh:SFIS were exposed during 8 weeks, 5 day per week to doses 0.05 Gy and 0.10 Gy of X-rays, 25 mg/kg mc and 50 mg/kg bw of nonylphenol as well as to 0.05 Gy + 25 mg/kg bw NP and 0.10 Gy + 50 mg/kg bw NP for combined exposure. Both X-rays and NP, acting alone induced micronuclei in reticulocytes and in polychromatic erythrocytes of mice. Combined X-rays-NP exposure of peripheral blood reticulocytes and bone marrow polychromatic erythrocytes caused enhanced frequency of micronuclei compared to the effect of each agent alone. In bone marrow reticulocytes, combined exposure in lower doses (0.05 Gy + 25 mg/kg bw NP) induced enhanced mutagenic effect. Contrary, after combined exposure to both agents in higher doses (0.10 Gy + 50 mg/kg bw NP), nonylphenol may protected DNA of reticulocytes against damage induced by X-rays.

Chloroquine (CHQ) is a commonly used antimalarial agent. We evaluated the genotoxic potential of CHQ using chromosome aberration (CA), micronucleus (MN), and sperm head abnormality (SA) assays in vivo in Swiss albino mice. The interaction between a low dose of radiation and CHQ, as well as the effect of vitamin C on CHQ-induced genotoxicity, was also evaluated. It was observed that CHQ induced CA, as well as MN, in the bone marrow cells under certain treatment conditions. Further, CHQ induced significant increase in the frequency of SA both at 24 hr and 21 days of the treatment. In the present study vitamin C pretreatment apparently reduced the frequency of CA, MN, and SA induced by CHQ. In the combination studies with radiation and CHQ, we found that exposure to low doses of radiation (0.5 Gy) either prior to or following CHQ treatment, in the dose ranges tested, has little or no synergistic effect in the mutagenic evaluations in somatic cells. However, radiation exposure along with CHQ treatment resulted in significant increase in the frequency of SA as compared to the groups receiving CHQ alone at 21 days of the treatment. In summary, CHQ has the potential to induce genotoxicity in mammalian cells. Further, germ cells may be relatively more sensitive as compared to the somatic cells.

Hormone-sensitive lipase (HSL, Lipe, E.C.3.1.1.3) functions as a triglyceride and cholesteryl esterase, supplying fatty acids, and cholesterol to cells. Gene-targeted HSL-deficient (HSL(-/-)) mice reveal abnormal spermatids and are infertile at 24 weeks after birth. The purpose of this study was to follow the evolution of spermatid abnormalities as HSL(-/-) mice age, characterize sperm motility in older HSL(-/-) mice, and determine if mice expressing a human testicular HSL transgene (HSL(-/-)ttg) produce normal motile sperm. In situ hybridization indicated that HSL is expressed exclusively in steps 5-16 spermatids, but not in Sertoli cells. In HSL(-/-) mice, abnormalities were evident in step 16 spermatids at 5 weeks after birth, with defects progressively increasing in spermatids with age. The defects included multinucleation of spermatids, abnormal shapes and a reduction of elongating spermatids. In older HSL(-/-) mice, sperm counts appeared reduced by 42%, but this value was lower because samples were compromised by the presence of small degenerating germ cells in addition to sperm, both of which appeared of similar size and density. Sperm motility was dramatically reduced with only 11% classified as motile in HSL(-/-) mice compared to 76-78% of sperm in wild-type and HSL(-/-)ttg mice. Sperm morphology, counts, and motility were normal in HSL(-/-)ttg mice, as was their fertility. Collectively, the data indicate that HSL deficiency results in abnormal spermatid development with defects arising at 5 weeks of age and progressively increasing at later ages. HSL(-/-) mice also show a dramatic reduction in sperm counts and motility and are infertile. Mol. Reprod. Dev.(c) 2007 Wiley-Liss, Inc.