Inversion of genetic predisposition to carcinogenesis in liver of two lines of mice selected for resistance (Car-R) or susceptibility (Car-S) to skin carcinogenesis.
Two lines of mice, one resistant (Car-R) and one susceptible (Car-S) to skin carcinogenesis, were produced by bi-directional selective breeding. To see whether the characteristics of susceptibility or resistance to tumorigenesis were also expressed in the liver and lung, the two lines were submitted comparatively to treatment with 5,9-dimethyl dibenzo[c,g]carbazole (DiMeDBC), a potent hepatocarcinogenic derivative of the ubiquitous heterocyclic carcinogenic pollutant, 7H-dibenzo[c,g]-carbazole (DBC). An inversion of genetic predisposition to carcinogenesis in liver was observed. Car-R animals displayed rapid tumorigenesis in 100% of cases while Car-S mice were remarkably less sensitive, showing a 4-fold lower mean tumor multiplicity and a 4-month longer latency time. In parallel adduct formation by DiMeDBC and DBC in liver DNA was analyzed by the 32P-postlabeling method, showing a remarkably higher level in Car-R mice than in Car-S animals. These data indicate that tissue-specific sensibility in carcinogenesis may involve gene expression at various levels.
Service de Génotoxicité et Cancérogénèse, Institut Curie-Recherche, Centre Universitaire, Orsay, France. gentox&k@curie.u-psud.fr
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Périn
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Périn-Roussel
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Taras-Valéro
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Mouton
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Covelli
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Zajdela
D000818:Animals; D002227:Carbazoles / Q000009:adverse effects; D002273:Carcinogens / Q000009:adverse effects; D018736:DNA Adducts / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D012878:Skin Neoplasms / Q000235:genetics*
D002227:Carbazoles; D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; C039387:5,9-dimethyldibenzo(c,g)carbazole