Influence of age,sex and strain on the in vitro induction of unscheduled dna synthesis in rat hepatocyte primary cultures |
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Authors: | Gregory S Probst Leo E Hill |
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Institution: | (1) Toxicology Division Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, Indiana;(2) Toxicology Division, Lilly Research Laboratories, 46140 Greenfield, IN |
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Abstract: | The activity of chemical-induced unscheduled DNA synthesis was evaluated in hepatocyte primary cultures from Fischer 344 and Sprague-Dawley rats over a period of two years. In this two-year study hepatocytes from both sexes and strains were prepared from animals 2, 8, 14, 20 and 25 months of age and UDS was measured by autoradiography following treatment with N-methyl-AP-vitro-N-nitrosoguanidine and 2-acetylaminofluorine. A dose-related positive response occurred for both compounds throughout the study in hepatocytes from male and female Fischer rats and male Sprague-Dawley rats. The magnitude of the response was greatest in hepatocytes from male Fischer rats and a markedly lower response in unscheduled DNA synthesis occurred in all cultures prepared from animals of both strains and sexes at 20 and 25 months of age. Hepatocytes from female Sprague-Dawley rats showed a low level of unscheduled DNA synthesis with N-methylN-vitro-N-nitrosoguanidine throughout the study. The most striking finding was the absence of a UDS response to 2-acetylaminofuorene by hepatocytes from Sprague-Dawley females at the 8, 14, 20 or 25 month periods. The results indicate an age-related decrease in chemical-induced unscheduled DNA synthesis activity among rats.Abbreviations 2AAF
2-acetylaminofluorinedeDMSO]
- dimethylsulfoxide
3H-TdR, meth yl-3H-thymidine
- MNNG
N-methyl-N-vitro-N-nitrosoguanidine
- UDS
unscheduled DNA synthesis |
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Keywords: | age rat hepatocytes sex strain unscheduled DNA synthesis |
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