Quantitative estimation of susceptibility of aged animal to a mutagen in ambient air.

点击翻译按钮获取中文摘要

To clarify whether susceptibility to mutagens is altered during ageing, we analyze the mutation induced by benzo[a]pyrene (BaP) in the lungs of aged gpt delta mice, a model animal for detecting in vivo mutagehesis. One milligram of BaP was given intratracheally into the lung of gpt delta mice of 3,11 and 24 month (mo.) old (young, middle and old age, respectively), and mutant frequency (MF) was determined 14 days after administration. In the control mice, MF was increased depending on ageing from 0.7 x 10-5 (3 mo.) to 1.1 x 10-5 (11 mo.) but was not elevated at 24 mo.. In BaP-treated mice, MF was highest at 3.mo. (2.7 x 10-5) and decreased at 11 mo. (1. 7 x 10-5), but gradually increased at 24 mo.. MF in BaP-treated mice was 3, 9-,1.4-and 2.3-fold higher than that in the control mice at 3 mo., 11 mo. and 24 mo.. These observation showed that susceptibility to BaP was highest at young age and was reduced at middle age but was elevated again at old age.Mutation spectrum was drastically altered depending on the ageing. In the control mice, G>A transition was markedly increased at 11 mo. and 24 mo. On the other hand, in BaP treated mice, G>T transversion was a major mutation at 3 mo.. This base substitution was decreased depending on ageing but G>A transition was increased. Analysis of expression of drug metabolizing enzyme showed that the level of glutathione-S-transferase (GST) α in BaP treated mouse lungs was decreased depending aging and it became to be the same as that in the control at 24 mo.. The level of GST π was elevated depending on ageing but there was no significant between BaP treated mice and age-matched control. We did not observe the relationship between MF and the expression level of drug-metabolizing enzyme.