丙烯醛-DNA加合物的研究进展

REVIEW:THE FORMATION AND MUTAGENESIS OF ACROLEIN-DNA ADDUCTS

丙烯醛是一种活泼的α,β不饱和醛,在环境中广泛存在,香烟烟气和厨房油烟是人体丙烯醛暴露的主要环境来源.另一方面机体内丙烯醛可以通过脂质过氧化、氨基酸氧化等多种途径自发生成.进入人体后,丙烯醛和DNA发生加合生成丙烯醛-DNA加合物.目前研究最多的是丙烯醛-dG加合物,包括α-OH-PdG和γ-OH-PdG,其中γ-OH-PdG是主要dG加合物,可引起基因突变(约1%),以G→T突变为主,而次要加合物α-OH-PdG的突变概率高于γ-OH-PdG(约8%),同样以G→T突变为主,并且这些加合物与一些癌症密切相关,如吸烟相关肺癌和膀胱癌等.此外,丙烯醛可以与其它碱基发生加合,生成其它类型的DNA加合物,包括丙烯醛-dA、dC和dT加合物,其中一些加合物的结构已表征,并在体外反应中存在.

Acrolein,one of the most reactive α,β unsaturated aldehydes,is an ubiquitous environmental pollutant and is found in cigarette smoking and cooking.On the other hand,acrolein can also be endogenously released during lipid peroxidation,myeloperoxidase-mediated degradation of amino acids,and so on.Acrolein can directly react with DNA without metabolic activation.As a result several types of DNA adducts could be produced.Currently,most of studies focus on Acrolein-dG adduct,including α-OH-PdG and γ-OH-PdG.The measured amount of γ-OH-PdG is higher than α-OH-PdG in human body and it can generate about 1% gene mutation,while gene mutation frequency is 8% for α-OH-PdG.Both adducts mainly induce G→T mutation.In addition,other base adducts may also be generated in vitro,including Acrolein-dA,dC,and dT adducts.But their metabolism and genotoxicity are unknown.To unbiasedly judge the genotoxicity of acrolein,the formation,metabolism and genotoxicity of non-dG adducts should be considered.