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苯并[a]芘的诱变代谢产物在C57和DBA小鼠品系中的代谢及尿排泄

Metabolism and urinary excretion of mutagenic metabolites of benzo[a]pyrene in C57 and DBA mice strains.

作者信息

Camus A M, Aitio A, Sabadie N, Wahrendorf J, Bartsch H

出版信息

Carcinogenesis. 1984 Jan;5(1):35-9. doi: 10.1093/carcin/5.1.35.

Abstract

Groups of C57Bl/6 (B6) mice (responsive) and DBA/2 (D2) (non-responsive) mice received an i.p. dose of benzo[a]pyrene (BP) (100 mg/kg body weight) with or without pretreatment with beta-naphthoflavone (BNF), an inducer of monooxygenases. The amount of mutagenic BP metabolites in the urine was determined by the Salmonella/microsome assay (strain TA100) and excretion of BP metabolites was quantified by h.p.l.c. After inducer treatment, the responsive mice excreted more mutagens and total oxidized BP metabolites in the urine than did the non-responsive strain. The ratio of BP diols:total oxidized metabolites was 0.42 in B6 mice and 0.72 in D2 mice and was not affected by inducer treatment. After a dose of [14C]BP, radioactivity was measured in the faeces for up to 7 days. The half-life of [14C]BP in the non-responsive D2 mice was about twice that in the responsive B6 mice. Our results agreed with a previously proposed model of the risk factors for toxic effects and/or the development of tumours after exposure to polycyclic aromatic hydrocarbons in responsive and non-responsive mouse strains.

摘要

将C57Bl/6(B6)小鼠(反应性)和DBA/2(D2)小鼠(无反应性)分为几组,分别腹腔注射苯并[a]芘(BP)(100毫克/千克体重),部分组在注射前用单加氧酶诱导剂β-萘黄酮(BNF)进行预处理。通过沙门氏菌/微粒体试验(TA100菌株)测定尿液中致突变性BP代谢物的含量,并通过高效液相色谱法定量BP代谢物的排泄量。诱导剂处理后,反应性小鼠尿液中排出的诱变剂和总氧化BP代谢物比无反应性品系更多。BP二醇与总氧化代谢物的比例在B6小鼠中为0.42,在D2小鼠中为0.72,且不受诱导剂处理的影响。给予一剂[14C]BP后,在长达7天的时间内测量粪便中的放射性。无反应性D2小鼠中[14C]BP的半衰期约为反应性B6小鼠的两倍。我们的结果与先前提出的关于反应性和无反应性小鼠品系接触多环芳烃后产生毒性作用和/或肿瘤发生风险因素的模型一致。

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