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

为了阐明对诱变剂的易感性是否会随着年龄的增长而改变，我们分析了苯并[a]芘（BaP）在老龄gpt delta小鼠肺中诱导的突变，gpt delta小鼠是一种检测体内诱变的模型动物。给3、11、24月龄gpt delta小鼠（分别为青年、中年、老年）肺内灌胃1毫克BaP，给药后14天测定突变频率（MF）。在对照小鼠中，随着年龄的增长，MF从0.7 × 10-5（3个月）增加到1.1 × 10-5（11个月），但在24个月时没有升高。在bap处理的小鼠中，MF在3个月时最高。（2.7 × 10-5）， 11个月时下降。7 × 10-5)，但在24个月时逐渐增加。在3个月、11个月和24个月时，bap处理小鼠的MF比对照小鼠高3倍、9倍、1.4倍和2.3倍。这些观察表明，对BaP的易感性在年轻时最高，在中年时降低，但在老年时再次升高。随着年龄的增长，突变谱发生了巨大的变化。在对照小鼠中，G>T转位在11个月和24个月时显著增加。另一方面，在BaP处理的小鼠中，G>T转位是3个月时的主要突变。这种碱基取代随老化而减少，但G>A转变增加。药物代谢酶表达分析显示，BaP处理小鼠肺中谷胱甘肽- s -转移酶(GST) α水平随年龄的增长而下降，24月龄时与对照组基本持平。GST π水平随衰老而升高，但BaP处理的小鼠与年龄匹配的对照组之间没有显著性差异。我们没有观察到MF与药物代谢酶表达水平的关系。

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.