A Comparison of the Effects of 3'-Methyl-4-dimethylaminoazobenzene, 2-Methyl-4-dimethylaminoazobenzene, and 2-Acetylaminofluorene on Rat Liver DNA Stability and New Synthesis

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Abstract

The objective of the present study was to define early biochemical changes occurring in livers of rats that were fed various chemical carcinogens. Rats were subjected to partial hepatectomy and subsequently given multiple injections of radioactive thymidine to prelabel DNA in their liver. Following a 4-week recovery period the rats were placed on either basal diets or diets containing either 0.05% 3'-meth-yl-4-dimethylaminoazobenzene (3'-MeDAB), 0.028% 2-acetylaminofluorene, or 0.05% 2-methyl-4-dimethylaminoazobenzene for various periods. After 5 weeks 3'-MeDAB had caused a dose-dependent loss of prelabeled DNA demonstrating the cytotoxicity of this carcinogen. The comparatively noncarcinogenic 2-methyl-4-dimethylaminoazobenzene caused only a small loss of prelabeled DNA. In contrast, the hepatocarcinogen 2-acetylaminofluorene did not cause a loss of prelabeled DNA, demonstrating its low cytotoxicity. Autoradiography and histology revealed that the loss of prelabeled DNA in livers of rats fed 3'-MeDAB was largely due to parenchymal cell death. Experiments designed to separate liver regenerative hyperplasia from neoplastic hyperplasia revealed the presence of both an early and a delayed elevation of thymidine incorporation into liver DNA in rats fed 0.05% 3'-MeDAB. An “early” elevation of incorporation occurred during and shortly after 3'-MeDAB feeding, and a “delayed” elevation of incorporation occurred some weeks after the dye was discontinued. Autoradiography revealed that parenchymal cells were largely responsible for the increased incorporation. Feeding of 2-methyl-4-dimethylaminoazobenzene depressed thymidine incorporation. A direct comparison of the effects of isomolar levels of 3'-MeDAB and 2-acetylaminofluorene on hepatic hyperplasia indicated that both carcinogens caused comparable increases in thymidine incorporation, which returned to control levels upon feeding.

Original languageEnglish (US)
Pages (from-to)1225-1234
Number of pages10
JournalCancer Research
Volume35
Issue number5
StatePublished - May 1975
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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