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The occurrence of second primary tumors after curative treatment or simultaneous multiple malignancies are current problem in head and neck cancer. The mutagen sensitivity is well known marker to predict patient proneness to develop the second tumor. The frequency and localization of spontaneous and mutagen induced chromatid breaks in peripheral blood lymphocytes (PBLs) in patients with multiple primary tumors (MPT) may help in defining regions involved in cancerogenesis process. The case control study using the bleomycin sensitivity assay (number of chromatid breaks per cell (b/c) was performed in 36 patients with MPT and two control groups: 52 patients with one malignancy and 47 healthy individuals. The differences between examined patients and control groups were estimated using U Mann-Whitney test. The b/c level in PBLs of patients with MPT ranged from 0.26 to 4.12 (mean 1.53) and was significantly higher (p<0.000006) both compared with patients with one malignancy (b/c ranged from 0.02 to 3.08; mean 0.74) and healthy controls (b/c ranged from 0.04 to 1.14; mean 0.41). An increase of b/c index was observed in almost all chromosomal arms. The majority of chromosomal locations with the increased proportion of breaks in the group of patients with multiple tumors were identified as regions where loci involved in DNA repair, cell cycle regulation suppressor genes and oncogenes were found. Statistically higher induced individual susceptibility in MPT patients compared with single tumor and healthy controls was confirmed. Comparable induced mean b/c was found in patients with two smoking-related cancers as well as with not smoking related tumors.

Monosomy 1p36 results from a variety of chromosome rearrangements, including terminal deletions, interstitial deletions, derivative chromosomes, and complex rearrangements. Our previous molecular studies on a large cohort of monosomy 1p36 subjects suggest that a significant percentage of terminal deletions of 1p36 are stabilized by the acquisition of telomeric sequences from other chromosome ends, forming derivative chromosomes (i.e., "telomere capture"). However, the molecular mechanism(s) that results in and/or stabilizes terminal deletions of 1p36 by telomere capture is poorly understood. In this report, we have mapped the translocation breakpoints in three subjects with der(1)t(1;1)(p36;q44) chromosomes by fluorescence in situ hybridization (FISH). These results indicate that the breakpoint locations are variable in all three subjects, with no common 1p deletion or 1q translocation breakpoints. In addition, sequence analysis of the 1p and 1q breakpoint-containing clones did not identify homologous sequences or low-copy repeats in the breakpoint regions, suggesting that nonallelic homologous recombination did not play a role in mediating these rearrangements. Microsatellite marker analysis indicates that two of the three derivative chromosomes were formed by intra-chromosomal rearrangements. These data are consistent with a number of recent reports in other model organisms that suggest break-induced replication at the site of a double-strand break may act as a mechanism of telomere capture by generating nonreciprocal translocations from terminally deleted chromosomes. Alternative models are also discussed.

Zearalenone (ZEA) is a macrocyclic lactone, estrogenic, diet-depending and fusaric micotoxin, which is produced on many kinds of cereals and feeds in the favourable conditions of humidity and temperature. The structure of ZEA is similar to the structure of estrogens and it enables binding to the estrogenic receptors. The stimulation of protein synthesis in the cells of the reproductive system, which causes intensification of cell proliferation, is one of the effects of ZEA actions. Oedema and vulva reddening are the clinical, external signs of ZEA intoxication in pigs. The aim of this study was to designate the degree of reproductive cell proliferation after low doses of ZEA were applied per os in sexually immature gilts with simultaneous monitoring of zearalenone and alpha-zearalenol levels in peripheral blood. The following were observed in the gilts examined fluctuations of zearalenone and alpha-zearalenol levels in blood, which were connected with entero-hepatic circulation and also numerous histopathological changes in ovarian follicle structure. These changes were present in the reproductive system of sexually immature gilts with a big contribution of PCNA-positive cells. The studies show that zearalenone application in sexually immature gilts caused ovarian follicle atresia and apoptoso-like changes in granule cells. Intensified cell proliferation, which was expressed with the growth of PCNA index, was observed in uterus and oviduct.

Arylamines are known bladder carcinogens deriving from tobacco smoke and environmental pollution. Arylamines are metabolised by NAT1 and NAT2 polymorphic enzymes in reactions of carcinogen activation and detoxification. We analysed genetic polymorphisms in both NAT1 and NAT2 genes in 56 bladder cancer patients and 320 healthy patients. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 (six alleles) and NAT2 (four alleles) by PCR-RFLP. A weak association between NAT1 and NAT2 genotypes and bladder cancer risk was found when the genotypes were estimated separately (odds ratio OR 1.2, 95%CI 0.7-2.0, and OR 1.3, 95%CI 0.7-1.9, respectively). Almost all NAT1 genotypes possessing at least one "risk" *10 allele were more frequent in the bladder cancer group than in the control group. There was also an increased frequency of "risk" genotypes along with increased cigarette smoking in bladder cancer patients. The coincidence of NAT1-fast/NAT2-slow appears as a potential risk factor for urinary bladder cancer (OR 1.5, 0.8-3.0), as compared with the other genotype combinations.

Polycyclic aromatic hydrocarbons (PAH) are a well-characterized group of mutagens and carcinogens. Benzo(a)pyrene [B(a)P], the best known compound in the group, exerts its genotoxic activity following metabolic activation, when it acquires the properties of an electrophilic reagent that is capable of interacting with DNA. Reactive oxygen species (ROS) can remerge during the PAH metabolic activation. Because of their antioxidant activity, vitamins C and E are thought to act as antimutagenic agents. We designed an in vitro protocol to study the potential protective effect of vitamins C and E toward B(a)P-induced DNA damage. In this study, we examined peripheral blood lymphocytes obtained from healthy nonsmoking female volunteers, 22 to 25 years of age. The cells were exposed in vitro to 1 microM B(a)P in the presence of 40 microM or 100 microM of vitamin C or, alternatively, to 30 microM or 100 microM of vitamin E. The B(a)P-induced DNA damage and repair were estimated as the generation and removal of single-strand DNA breaks measured by the alkaline version of the single-cell gel electrophoresis (comet) assay. The protective effect of vitamins C and E was demonstrated when the vitamins were applied simultaneously with or after the B(a)P. The background level of DNA damage in the presence of vitamins C and E was lower than in the system without the vitamins. The experiments were conducted according to various protocol schemes of the vitamin treatment and the results offer additional evidence of the antigenotoxic activity of vitamins C and E. The vitamin activity does not appear to be connected with the steps in metabolic activation or DNA repair. It seems that both vitamins act as competitors of DNA molecule in reaction with the reactive oxygen species.