Morphological cell transformation and DNA adduction by benz(j)aceanthrylene and its presumptive reaction metabolites in C3H10T1/2CL8 cells.

Morphological cell transformation and DNA adduction by benz(j)aceanthrylene and its presumptive reaction metabolites in C3H10T1/2CL8 cells.
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C3H10T1/2CL8 细胞中苯并苊及其假定反应代谢物的形态细胞转化和 DNA 加合。

DOI:
10.1007/978-1-4684-5877-0_101
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发表时间:
1991
影响因子:
--
通讯作者:
Nesnow,S
Nesnow,S
中科院分区:
医学4区
文献类型:
--
作者:
Lasley,J;Curti,S;Ross,J;Nelson,G;Sangaiah,R;Gold,A;Nesnow,S

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Benz(j)醋蒽烯[B(j)A],一种在煤燃烧排放物中发现的环戊稠合多环芳烃[Grimmer等人,1985;施密特等人,1986],是C3 H10 T1/2CL 8(C3 H10 T1/2)小鼠胚胎成纤维细胞中形态转化活性的强诱导剂[Mohapatra等人,1987年]。研究了这些细胞对B(j)A的代谢,结果与Aroclor-1254诱导的大鼠肝S9不同。在C3 H10 T1, 2细胞中,主要代谢物是9,10-二氢-9,10-二羟基-B(j)A和少量的1,2-二氢-1,2-二羟基-B(j)A [Mohapatra等人,1987],而在大鼠肝脏S9中,主要代谢产物为1,2-二氢-1,2-二羟基-B(j)A [Nesnow等人,1988年]。这些结果表明,虽然Aroclor-1254诱导的大鼠肝脏S9代谢活化的主要途径是通过B(j)A-1,2-氧化物(环戊环上的芳烃氧化物),但B(j)A在C3 H10 T1/2细胞中的代谢活化可能通过两种途径:形成氧化波他烯[B(j)A-1,2-氧化物]和湾区二醇-环氧化物[9,10-二氢-9,10-二羟基-B(j)A-7,8-氧化物]。本研究旨在阐明推定的反应性中间体9,10-二氢-9,10-二羟基-B(j)A-7,8-氧化物[B(j)A-二醇-环氧化物]和B(j)A-1,2-氧化物在C3 H10 T1/2细胞中B(j)A代谢活化中的作用。
Benz(j)aceanthrylene [B(j)A], a cyclopenta-fused polycyclic aromatic hydrocarbon found in coal combustion emissions [Grimmer et al., 1985; Schmidt et al., 1986], is a strong inducer of morphological transforming activity in C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts [Mohapatra et al., 1987]. The metabolism of B(j)A by these cells has been studied and the results differ from those found with Aroclor-1254 induced rat liver S9. In C3H10T1/2 cells the major metabolite is 9,10dihydro-9,10-dihydroxy-B(j)A with minor amounts of 1,2-dihydro-1,2-dihydroxy-B(j)A [Mohapatra et al., 1987], while in rat liver S9 the major metabolite is 1,2-dihydro-1,2-dihydroxy-B(j)A [Nesnow et al., 1988]. These results suggest that while the major route of metabolic activation by Aroclor-1254 induced rat liver S9 is through B(j)A-1,2-oxide, the arene oxide at the cyclopenta-ring, metabolic activation of B(j)A in C3H10T1/2 cells might be via two routes: botharene oxide [B(j)A-1,2-oxide] formation and bay-region diol-epoxide formation [9,10-dihydro-9,10-dihydroxy-B(j)A-7,8-oxide]. This study was undertaken to clarify the role of the putative reactive intermediates, 9,10-dihydro-9,10-dihydroxy-B(j)A-7,8-oxide [B(j)A-diol-epoxide], and B(j)A-1,2-oxide in the metabolic activation of B(j)A in C3H10T1/2 cells.