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1357660 
Journal Article 
Mutation and Neoplastic Transformation. Correlations and Dissociations 
Barrett, JC; Oshimura, M; Tsutsui, T; Tanaka, N 
1988 
Yes 
Annals of the New York Academy of Sciences
ISSN: 0077-8923
EISSN: 1749-6632 
NIOSH/00185932 
534 
95-98 
English 
The somatic mutation theory of carcinogenesis has been used as the basis for most short term tests for carcinogens. Good experimental data supported this theory based on molecular and cytogenic analysis of mutational changes in tumors. Even so, certain chemicals have been defined as nonmutagenic carcinogens. Several mechanisms for the lack of detectable mutagenic activity of these carcinogens were discussed. One example was amitrole (61825), which was inactive as a mutagen in bacterial test systems, but was mutagenic in Syrian-hamster embryo cells. The organotropism of amitrol was explained by the metabolic activation of this chemical to reactive intermediates in combination with a hormone like action on the thyroid. Other apparent exceptions to the correlation between carcinogenicity and mutagenicity such as benzene (71432), arsenic (7440382), diethylstilbestrol (56531), and asbestos (1332214) may involve the ability of certain chemicals to act specifically as chromosome mutagens. The methylation of DNA at the 5 position of cytosine was found to be important in the regulation of gene expression and was one possible mechanism for the heritable change in cancer cells that does not require a direct interaction between the carcinogen and DNA. Some chemicals exerted a carcinogenic effect due in part to their tumor promoting activity. Such activity should not be viewed as mutually exclusive of genetic activity in the same chemical. 
DCN-176637; Nucleic acids; Genotoxic effects; Neoplastic transformation; Tumorigenesis; Heavy metals; Gene mutation; Oncogenesis 
Selikoff, I. J.