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Chronic ingestion of clastogens by mice and the frequency of chromosome aberrations
Author(s) -
Director Alison E.,
Tucker James D.,
Ramsey Marilyn J.,
Nath Joginder
Publication year - 1998
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1998)32:2<139::aid-em9>3.0.co;2-o
Subject(s) - mutagen , clastogen , carcinogen , ingestion , micronucleus test , toxicity , chromosomal translocation , in vivo , toxicology , chronic toxicity , biology , micronucleus , bone marrow , physiology , genotoxicity , chemistry , genetics , medicine , immunology , endocrinology , gene
Environmental exposure to mutagens is believed to play a significant role in human carcinogenesis. Determination of the in vivo effects of a single mutagen is best done in laboratory animals because humans are exposed to a variety of mutagens both in their diet and in the rest of their environment. In this study, C57BL/6N female mice were used to analyze the effect on chromosomes of chronic ingestion of a mutagen dissolved in drinking water. Cyclophosphamide (CP) or urethane (ethyl carbamate, EC) were dissolved in sterile drinking water at concentrations of 0, 32, 64, and 96 ppm or 0, 5,000, 10,000, and 15,000 ppm, respectively. All exposures began at 8 weeks of age and continued through the 20th week unless terminated earlier due to toxicity. Body weights and water consumption were measured weekly. Blood and bone marrow were taken from approximately five mice per exposure group at 4, 8, and 12 weeks from the start of exposure. All mice remaining after 12 weeks received drinking water without any carcinogen for an additional 6 weeks to determine if induced aberrations persisted. Chromosome translocations, measured by painting, were not induced in blood or bone marrow cells at any time point for either chemical. However, both carcinogens induced significant increases in micronucleated normochromatic erythrocytes, indicating that the carcinogens reached the tissues examined in these experiments. These results indicate that chronic exposure of mice to chemical carcinogens induces chromosome breakage measurable by micronuclei. However, the breakage and reunion necessary to see chromosome exchanges such as translocations were not observed in this study. Environ. Mol. Mutagen. 32:139–147, 1998 © 1998 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.