Glatt H, Seidel A, Bochnitschek W, Marquardt H, Marquardt H, Hodgson R M, Grover P L, Oesch F
Cancer Res. 1986 Sep;46(9):4556-65.
The syn- and anti-isomers of the bay-region diol-epoxides of chrysene and of 3-hydroxychrysene and their metabolic precursors have been investigated for mutagenicity in Salmonella typhimurium (reversion to histidine prototrophy) and V79 Chinese hamster cells (acquirement of resistance to 6-thioguanine) and for transforming activity in M2 mouse prostate cells. Other known and potential chrysene metabolites have been included in mutagenicity experiments. Direct mutagenic activity in S. typhimurium TA 100 exhibited, in order of potency, anti-triol-epoxide greater than syn-triol-epoxide greater than anti-diol-epoxide greater than syn-diol-epoxide greater than chrysene 5,6-oxide much greater than chrysene-1,2-quinone, chrysene-3,4-quinone, and chrysene 5,6-quinone. Chrysene, the six isomeric chrysenols, and the trans-dihydrodiols [trans-1,2-dihydroxy-1,2-dihydrochrysene (chrysene-1,2-diol), trans-3,4-dihydroxy-3,4-dihydrochrysene, trans-5,6-dihydroxy-5,6-dihydrochrysene, and 9-hydroxy-trans-1,2-dihydroxy-1,2-dihydrochrysene (9-hydroxychrysene-1,2-diol)] were inactive per se but were activated to mutagens in the presence of reduced nicotinamide adenine dinucleotide phosphate-fortified postmitochondrial fraction (S9 mix) of liver homogenate from Arochlor 1254-treated rats. Chrysene, 3-hydroxychrysene, chrysene-1,2-diol, and 9-hydroxychrysene-1,2-diol were activated efficiently; the other compounds were activated weakly. In S. typhimurium TA 98, the mutagenic activities of the chrysene derivatives were weak in comparison with those in the strain TA 100. trans-3,4-Dihydroxy-3,4-dihydrochrysene (in the presence of S9 mix) was the most efficacious mutagen in strain TA 98. The relative mutagenic potencies of the directly active compounds differed from the results obtained in strain TA 100, in that in strain TA 98 the anti-diol-epoxide was more mutagenic than the triol-epoxides and chrysene 5,6-oxide was more mutagenic than syn-diol-epoxide and syn-triol-epoxide. In V79 cells, the order of mutagenic potency was: anti-triol-epoxide greater than anti-diol-epoxide greater than syn-triol-epoxide greater than syn-diol-epoxide greater than chyrsene 5,6-oxide greater than chrysene-1,2-diol (in the presence of S9 mix) greater than 9-hydroxychrysene-1,2-diol (in the presence of S9 mix) greater trans-3,4-dihydroxy-3,4-dihydrochrysene in the presence of S9 mix). Chrysene, 3-hydroxychrysene, 5-hydroxychrysene, and 6-hydroxychrysene showed no mutagenic effects in V79 cells, either in the presence or absence of S9 mix.(ABSTRACT TRUNCATED AT 400 WORDS)
对芘及3-羟基芘的湾区二醇环氧化物的顺式和反式异构体及其代谢前体进行了研究，检测其在鼠伤寒沙门氏菌（回复为组氨酸原养型）和V79中国仓鼠细胞（获得对6-硫鸟嘌呤的抗性）中的致突变性，以及在M2小鼠前列腺细胞中的转化活性。其他已知和潜在的芘代谢产物也被纳入致突变性实验。在鼠伤寒沙门氏菌TA 100中，直接致突变活性按效力顺序为：反式三醇环氧化物大于顺式三醇环氧化物大于反式二醇环氧化物大于顺式二醇环氧化物大于芘5,6-氧化物远大于芘-1,2-醌、芘-3,4-醌和芘5,6-醌。芘、六种异构的芘醇以及反式二氢二醇[反式-1,2-二羟基-1,2-二氢芘（芘-1,2-二醇）、反式-3,4-二羟基-3,4-二氢芘、反式-5,6-二羟基-5,6-二氢芘和9-羟基-反式-1,2-二羟基-1,2-二氢芘（9-羟基芘-1,2-二醇）]本身无活性，但在来自经Arochlor 1254处理的大鼠肝脏匀浆的还原型烟酰胺腺嘌呤二核苷酸磷酸强化的线粒体后组分（S9混合液）存在下被激活为诱变剂。芘、3-羟基芘、芘-1,2-二醇和9-羟基芘-1,2-二醇被高效激活；其他化合物被微弱激活。在鼠伤寒沙门氏菌TA 98中，芘衍生物的致突变活性与在TA 100菌株中的相比很弱。反式-3,4-二羟基-3,4-二氢芘（在S9混合液存在下）是TA 98菌株中最有效的诱变剂。直接有活性的化合物的相对致突变效力与在TA 100菌株中获得的结果不同，在TA 98菌株中，反式二醇环氧化物比三醇环氧化物更具致突变性，芘5,6-氧化物比顺式二醇环氧化物和顺式三醇环氧化物更具致突变性。在V79细胞中，致突变效力顺序为：反式三醇环氧化物大于反式二醇环氧化物大于顺式三醇环氧化物大于顺式二醇环氧化物大于芘5,6-氧化物大于芘-1,2-二醇（在S9混合液存在下）大于9-羟基芘-1,2-二醇（在S9混合液存在下）大于反式-3,4-二羟基-3,4-二氢芘（在S9混合液存在下）。芘、3-羟基芘、5-羟基芘和6-羟基芘在V79细胞中，无论有无S9混合液，均未显示致突变作用。（摘要截断于400字）
