Yu Hongtao, Yan Jian, Jiao Yuguo, Fu Peter P
Department of Chemistry, Jackson State University, Jackson, MS 39217, USA.
Int J Environ Res Public Health. 2005 Apr;2(1):114-22. doi: 10.3390/ijerph2005010114.
DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.
7,12-二甲基苯并[a]蒽（DMBA）是一种经过广泛研究的多环芳烃，长期以来一直被认为是一种可能的人类致癌物。现已发现，DMBA在细菌以及动物或人类细胞中具有光毒性，并且在鼠伤寒沙门氏菌TA102菌株中具有光致突变性。本文试图解释其光化学和光致突变性机制。光照可将DMBA转化为多种光产物，包括苯并[a]蒽-7,12-二酮、7-羟基-12-酮-7-甲基苯并[a]蒽、7,12-环氧-7,12-二氢-DMBA、7-羟甲基-12-甲基苯并[a]蒽和12-羟甲基-7-甲基苯并[a]蒽。这些光产物结构已通过与标准样品比较或核磁共振/质谱法得以鉴定。至少还有四种其他光产物有待确定。在小牛胸腺DNA存在的情况下同样对DMBA进行光照射，并通过32P后标记/薄层色谱法分析光诱导的DMBA-DNA加合物，这表明形成了多种DNA加合物。这表明DNA加合物的形成可能是DMBA光致突变性的来源。用大鼠肝微粒体对DMBA进行代谢获得的代谢产物与小牛胸腺DNA反应，并在相同条件下通过32P后标记/薄层色谱法分析所得的DNA加合物。DNA加合物图谱的比较表明，光照射形成的DNA加合物与DMBA代谢产物与DNA反应形成的DNA加合物不同。这些结果表明，DMBA的光照射可通过与DMBA微粒体代谢不同的激活途径导致遗传毒性。
