The effect of pyrazole, phenobarbital, ethanol and 3-methylcholanthrene pretreatment on the in vivo and in vitro genotoxicity of N-nitrosopyrrolidine.
The effect of pyrazole, phenobarbital, ethanol and 3-methylcholanthrene pretreatment on the in vivo and in vitro genotoxicity of N-nitrosopyrrolidine.
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吡唑、苯巴比妥、乙醇和3-甲基胆蒽预处理对N-亚硝基吡咯烷体内外遗传毒性的影响。
DOI：
10.1093/carcin/9.6.1001
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发表时间：
1988
期刊：
影响因子：
4.7
通讯作者：
Brunk,G
中科院分区：
文献类型：
--
作者：
Gold,B;Brunk,G
本文研究了N-亚硝基吡咯烷对鼠伤寒沙门氏菌TA1535株的体外遗传毒性，以及经吡唑、苯巴比妥(PB)、4天乙醇(EtOH)、10天乙醇和3-甲基胆蒽(3-MC)处理的雄性SD大鼠肝脏S-9组分的毒性。除非另有说明，最后一次预暴露是在处死和分离肝酶前24小时。吡唑和乙醇(10天)均能有效地诱导神经肽Y转化为诱变剂。PB和乙醇(4天)对回复突变数有一定的促进作用，而3-MC和未诱导的S-9组分的结果与背景组分(无神经肽Y)无显著差异。采用相同的前处理方案，用碱性洗脱技术测定NPY对大鼠肝脏的毒性。诱导剂在活体动物中的作用与对照组完全相反，3-MC和4天乙醇处理的动物显示出最高水平的DNA损伤。吡唑和10天的乙醇预处理使DNA洗脱速率常数与未经NPY处理的动物相当。然而，在10天的乙醇预处理动物中，在乙醇和NPY暴露之间没有24小时间隔的情况下，观察到与未诱导和3-MC处理的大鼠相同的高水平的DNA损伤。从微体蛋白的解毒作用和活体DNA损伤可能是由与核室相关的酶诱导的角度对结果进行了讨论。
Thein vitrogenotoxicity ofN-nitrosopyrrolidine (NPy) has been studied inSalmonella typhimuriunstrain TA1535 in the presence of untreated and pyrazole-, phenobarbital (PB)-, 4-day ethanol (EtOH)-, 10-day EtOH- and 3-methylcholanthrene (3-MC)-pretreated male Sprague — Dawley rat liver S-9 fractions. Unless stated otherwise, the last pretreatment exposure was 24 h prior to sacrifice and isolation of hepatic enzymes. Pyrazole and EtOH (10-day exposure) both effectively induced the conversion of NPy into a mutagen at doses as low as 500 μM. PB and EtOH (4-day exposure) had a modest enhancing effect on the number of revertants scored, while 3-MC and uninduced S-9 fractions gave results not significantly different from background (no NPy). The same pretreatment protocols were used to determine thein vivogenotoxicity of NPy in rat liver using the technique of alkaline elution. The inducing agents had the exact opposite effectin vivowith control, 3-MC- and 4-day EtOH-treated animals showing the highest level of DNA damage. Pyrazole and 10-day EtOH pretreatments gave DNA elution rate constants comparable to animals not treated with NPy. However, in 10-day EtOH-pretreated animals which were administered NPy without a 24-h interval between EtOH and NPy exposure, DNA damage was observed at the same high levels as was seen in uninduced and 3-MC treated rats. The results are discussed in terms of a detoxification role for microsomal proteins and that the observedin vivoDNA damage may be induced by enzymes associated with the nuclear compartment.