Bedard Leanne L, Massey Thomas E
Department of Pharmacology and Toxicology, Queen's University, Botterell Hall, Kingston, Ont., Canada K7L 3N6.
Cancer Lett. 2006 Sep 28;241(2):174-83. doi: 10.1016/j.canlet.2005.11.018. Epub 2006 Feb 3.
Aflatoxin B(1) (AFB(1))-N(7)-guanine is the predominant adduct formed upon the reaction of AFB(1)-8,9-exo-epoxide with guanine residues in DNA. AFB(1)-N(7)-guanine can convert to the ring-opened formamidopyrimidine, or the adducted strand can undergo depurination. AFB(1)-N(7)-guanine and AFB(1)-formamidopyrimidine are thought to be predominantly repaired by nucleotide excision repair in bacteria, yeast and mammals. Although AFB(1)-formamidopyrimidine is removed less efficiently than AFB(1)-N(7)-guanine in mammals, both lesions are repaired with equal efficiencies in bacteria, reflecting differences in damage recognition between bacterial and mammalian repair systems. Furthermore, DNA repair activity and modulation of repair by AFB(1) seem to be major determinants of susceptibility to AFB(1)-induced carcinogenesis.
黄曲霉毒素B1（AFB1）-N7-鸟嘌呤是AFB1-8,9-外环氧化物与DNA中的鸟嘌呤残基反应形成的主要加合物。AFB1-N7-鸟嘌呤可转化为开环的甲酰胺嘧啶，或者加合的链可发生脱嘌呤作用。在细菌、酵母和哺乳动物中，AFB1-N7-鸟嘌呤和AFB1-甲酰胺嘧啶主要通过核苷酸切除修复进行修复。尽管在哺乳动物中，AFB1-甲酰胺嘧啶的去除效率低于AFB1-N7-鸟嘌呤，但在细菌中这两种损伤的修复效率相同，这反映了细菌和哺乳动物修复系统在损伤识别方面的差异。此外，DNA修复活性以及AFB1对修复的调节似乎是对AFB1诱导致癌作用易感性的主要决定因素。
