Mutagenesis of certain benzo(a)pyrene phenols in vitro following further metabolism by mouse liver.

Low concentrations of 1-hydroxy- and 3-hydroxybenzo[a]pyrene in the presence of NADPH and liver S-9 fraction from 3-methylcholanthrene-treated C57BL/6N mice are as much as 3-fold more mutagenic than benzo[a]pyrene in the bacteria Salmonella typhimurium LT₂ tester strain TA98. The level of mutagenicity rises with increasing phenol or S-9 protein concentration. In this system, 9-hydroxy-benzo[a]pyrene is slightly mutagenic, while 2-hydroxy-, 7-hydroxy- and 12-hydroxybenzo[a]pyrene are not mutagenic at low concentrations. The S-9 fraction from 3-methylcholanthrene-treated DBA/2N mice or phenobarbital-treated C 5 7BL/6N mice does not support significant levels of mutagenesis. The high level of mutagenicity by 1-hydroxy- or 3-hydroxybenzo[a]pyrene is inhibited by α-naphthoflavone but is not inhibited by metyrapone, 1, 2-epoxy-3, 3, 3-trichloropropane or glutathione. The substrate for UDP-glucuron-osyltransferase, UDP-glucuronic acid, prevents more than half of the mutagenicity caused by the further metabolism of 1-hydroxy- and 3-hydroxybenzot alpyrene. The combination of UDP-glucuronic acid and UDP-N-acetylglucosamine provides an even higher level of protection. The addition of the substrate for sulfotransferase(s), 3'-phosphoadenosine 5'-phosphate sulfate, also prevents about half of the mutagenesis caused by 1-hydroxy- or 3-hydroxybenzo[a]pyrene.     

过氧化苯甲酰在诱发金黄地鼠舌癌中的作用

目的：证实在癌变过程中,促癌剂和诱癌剂同样有着重要作用。方法：本实验通过二甲基苯并蒽（ＤＭＢＡ）涂抹金黄地鼠舌粘膜,并用２０％过氧化苯甲酰局部涂抹同一部位,每周２次,共２０周。同样方法分别涂布ＤＭＢＡ（对照组）和２０％过氧化苯甲酰（阴性对照组）。结果：对照组成瘤率９０％（２７／３０）,而实验组为１００％（３０／３０）,２组动物均经历了上皮异常增生、原位癌、浸润及转移癌几个阶段,但实验组在每一阶段较     

Deoxyribonucleic acid binding of 3-hydroxy- and 9-hydroxybenzo[a]pyrene following further metabolism by mouse liver microsomal cytochrome P1-450.

In the presence of NADPH and microsomes from 3-methylcholanthrene-treated C57BL/6N mice, [³H]3-OH-benzo[a]pyrene is metabolized to reactive intermediates which covalently bind to deproteinized salmon sperm DNA in vitro. Enzymatically digested DNA, containing bound [³H]3-OH-benzolajpyrene derivatives, generates an elution profile from Sephadex LH20 chromatography which resembles similar chromatograms with [³H]benzo[a]pyrene. All peaks resulting from [³H]benzo[a]pyrene activation appear to be prominently represented in [³H]3-OH-benzo[a]pyrene activation, except that several peaks which emerge near the end of the eluting gradient of methanol and water are much reduced. Notably, a peak designated E, and attributed to benzo[a]pyrene-7, 8-diol-9, 10-oxide binding in [³H]benzo[a]pyrene incubations, is also prominently represented in incubations with [³H]3-OH-benzo[a]pyrene. Radioactivity in all of these peaks is inhibited effectively if one-seventh the concentration of 1-OH-benzo[a]pyrene is included in the incubation with [³H]3-OH-benzo[a]pyrene. Microsomes from 3-methylcholanthrene-treated DBA/ 2N mice cause insignificant binding. UDP-glucuronic acid markedly reduces all peaks except E, and 1, 2-epoxy-3, 3, 3-trichloropropane reduces all peaks except C and E. 9-Hydroxybenzo[a]pyrene is further metabolized to DNA binding species by microsomes from either 3-methylcholanthrene-treated DBA/2N or C57BL/6N mice. UDP-glucuronic acid prevents about 50 per cent of the binding with microsomes from DBA/2N mice but not with microsomes from C57BL/6N. In contrast, UDP-glucuronic acid does prevent binding in some of these same peaks when [³H]benzotaipyrene is the starting substrate with microsomes from C57BL/6N mice. UDP-glucuronic acid does not prevent binding in peak E in incubations with [³H]benzo[a]pyrene or [³H]3-hydroxybenzo[a]pyrene.     

环境与职业因素对胎儿生长发育的影响

为探讨环境与职业因素对胎儿生长发育的影响，对５７２例孕妇进行回顾性调查，单因素分析结果提示：孕妇暴露于苯系混合物在家被动吸烟能使新生儿出生体重及身长降低，与对照组比较差异具有显著性，孕妇摄食蛋白，鱼类，肉类，奶类增多，有促使新生儿出生体重，身长增加的趋势，多因素逐步回归分析结果提示：在多种职业及环境因素并存的情况下，诸因素之间存在联合作用，孕妇苯系混合物暴露是影响胎儿生长发育的主要因素，而孕妇被动     

苯作业者遗传毒性效应的研究

本文选择遗传学效应的染色体畸变、染色体姊妹单体互换(SCE)和微核率三指标对苯作业人群进行检测。结果表明:苯作业者在苯浓度超标的状态下工作,可导致染色体畸变率、SCE和微核率增高。且在白细胞下降前即可出现。尤其以SCE最为敏感并且与白细胞的损伤相关。建议苯的慢性毒效应检测应加入遗传学效应指标。