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Several reports described an age-related accumulation of a particular mitochondrial DNA (mtDNA) deletion (`common deletion') in post-mitotic tissues. These findings led to the hypothesis that free radicals generated inside the mitochondria could damage mtDNA during a normal life span. The impaired electron transfer function resulting from mtDNA damage would increase the production of free radicals...
Rearrangements in the vicinity of the centromere of chromosome 1 are over-represented in many types of human cancer and are a characteristic feature of a rare genetic disease called ICF (immunodeficiency, centromeric heterochromatin instability, and facial anomalies). Evidence is presented that implicates DNA hypomethylation in the formation of these pericentromeric chromosomal anomalies. The DNA...
The environmental contaminants 1- and 3-nitrobenzo[a]pyrene (1- and 3-nitro-BaP) are mutagens in Chinese hamster ovary (CHO) cells with exogenous metabolic activation. Previous studies demonstrated the potent direct-acting mutagenicity of the oxidized metabolites, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-1-nitrobenzo[a]pyren e (1-NBaPDE) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo[a]pyren...
Graf et al. (U. Graf, F.E. Wurgler, A.J. Katz, H. Frei, H. Juon, C.B. Hall, P.G. Kale, Somatic mutation and recombination test in Drosophila, Environment Mutagen. 6 (1984) 153-188.) described the overall results of assays of a series of compounds in the Drosophila wing spot test as indicating that single mwh spots appeared most frequently, followed by less frequent twin spots with both mwh and flr...
Genotoxic effects linking cigarette smoking with lung cancer have not been consistently demonstrated, therefore claims for the cause-effect relationships are vigorously contested. Using matched populations of 22 lung cancer patients who have been cigarette smokers (LCP), 22 non-cancerous cigarette smokers (SC) and 13 non-smokers (NSC), we have applied the fluorescence in situ hybridization (FISH)...
Various aneugens were reported to induce structural chromosomal aberrations beside their influence on cell division and their aneugenic potential To assess, whether a relationship between disturbance of cell division and clastogenic potential exists, CHO cells were treated with the well-known aneugens colcemid, colchicine and vincristine and investigated for the induction of structural chromosomal...
Direct pulmonary instillation of 1,6-dinitropyrene (DNP) into male Fischer 344 rats results in a dose-dependent induction of lung tumors and 6-thioguanine-resistant (TG r ) T-lymphocytes. The treatment also results in DNP binding to dG in the lung and in T-lymphocytes. In the present study, we have examined the types of mutations associated with these responses to DNP. Sequencing of DNA amplification...
The study of somatic mutation frequency, particularly stem cell somatic mutation, is important to the understanding of mechanisms of carcinogenesis. The models currently in use for studies in stem cell tissues such as the colon infer the presence of stem cell somatic mutation from alteration in enzyme function, when this has shown to be mutagen dose dependent, restricted to the unit of clonal architecture,...
TSG-p53/Big Blue ( R) double transgenic mice offer a powerful tool for examining the effect of a p53 germline mutation on spontaneous somatic mutation in vivo. After sequencing the DNA-binding domain of the lacI gene, we previously reported no differences in mutant frequency between p53 nullizygous (-/-) and p53 wild-type (+/+) mice in liver, spleen and brain. However, jackpot mutations elsewhere...
The mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella typhimurium TA98 is inhibited by flavonoids with distinct structure-antimutagenicity relationships (Edenharder, R., I. von Petersdorff I. and R. Rauscher (1993) Antimutagenic effects of flavonoids, chalcones and structurally related compounds on the activity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and other heterocyclic...
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