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Enhanced susceptibility to a chemical carcinogen in rats carrying MHC‐linked genes influencing development ( GRC )
Author(s) -
Rao Kalipatnapu N.,
Shinozuka Hishashi,
Kunz Heinz W.,
Gill Thomas J.
Publication year - 1984
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910340120
Subject(s) - biology , carcinogenesis , cell growth , endocrinology , carcinogen , medicine , dna synthesis , bile duct , gene , microbiology and biotechnology , biochemistry , dna
In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC‐linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N‐2‐acetylaminofluorene (AAF), and the induction of gamma‐glutamyltranspeptidase (GGT)‐positive foci, bile‐duct proliferation and oval‐cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT‐positive foci (from three to six per section) and extensive bile‐duct and oval‐cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT‐positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bileduct or oval‐cell proliferation. Biochemical studies of the liver and testes showed that the grchomozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3 H‐thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.