Cytogenetic studies of mice chronically fed carcinogens
- Lawrence Livermore National Lab., CA (United States); and others
Over the past few years, we have carried out chronic feeding studies in C57BL/6 female mice. These experiments examined the effect of the chronic ingestion of a single chemical carcinogen on chromosomes. The carcinogens studied were PhIP,MeIQx, cyclophosphamide and urethane. These studies used traditional assays, such as SCEs and MN, as well as chromosome painting. In all four cases, the traditional assays showed an increase in the frequency of lesions, demonstrating that the chemicals, and/or their reactive metabolites, reached the target nuclei. This, however, seemed at odds with the data obtained from chromosome painting, which did not show an increase in the frequency of stable chromosome aberrations. This discrepancy between traditional assays and chromosome painting may be due to the nature of the lesions that each assay identifies. The traditional assays tend to identify lesions on the chromatid level, where as chromosome painting identifies lesions on the chromosome level requires two or more DNA double strand breaks occurring proximally in both time and space. In other words, for exposure to a chemical carcinogen to induce an increase in chromosome aberrations as measured by chromosome painting, the chemical, or its metabolites, would have to cause a large number of double strand breaks. By applying this logic to the data obtained from the four chronic feeding studies, one can infer that the chronic ingestion of chemical carcinogens does not result in the frequent formation of double strand breaks and therefore, does not result in the frequent formation of double strand breaks and therefore, does not result in increased frequencies of stable chromosome aberrations. We must, therefore, look elsewhere for the mechanism(s) underlying carcinogenesis due to chronic exposure to chemical carcinogens.
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 530833
- Report Number(s):
- CONF-9704100-; ISSN 0893-6692; CNN: Grant CA55861; TRN: 97:003016-0006
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 29, Issue Suppl.28; Conference: 28. annual meeting of the Environmental Mutagen Society, Minneapolis, MN (United States), 19-23 Apr 1997; Other Information: PBD: 1997
- Country of Publication:
- United States
- Language:
- English
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