Mutagenicity of acrolein and acrolein-induced DNA adducts.
Acrolein mutagenicity relies on DNA adduct formation. Reaction of acrolein with deoxyguanosine generates alpha-hydroxy-1, N(2)-propano-2'-deoxyguanosine (alpha-HOPdG) and gamma-hydroxy-1, N(2)-propano-2'-deoxyguanosine (gamma-HOPdG) adducts. These two DNA adducts behave differently in mutagenicity. gamma-HOPdG is the major DNA adduct and it can lead to interstrand DNA-DNA and DNA-peptide/protein cross-links, which may induce strong mutagenicity; however, gamma-HOPdG can be repaired by some DNA polymerases complex and lessen its mutagenic effects. alpha-HOPdG is formed much less than gamma-HOPdG, but difficult to be repaired, which contributes to accumulation in vivo. Results of acrolein mutagenicity studies haven't been confirmed, which is mainly due to the conflicting mutagenicity data of the major acrolein adduct (gamma-HOPdG). The minor alpha-HOPdG is mutagenic in both in vitro and in vivo test systems. The role of alpha-HOPdG in acrolein mutagenicity needs further investigation. The inconsistent result of acrolein mutagenicity can be attributed, at least partially, to a variety of acrolein-DNA adducts formation and their repair in diverse detection systems. Recent results of detection of acrolein-DNA adduct in human lung tissues and analysis of P53 mutation spectra in acrolein-treated cells may shed some light on mechanisms of acrolein mutagenicity. These aspects are covered in this mini review.
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, PR China.
Xing-yu
XY
Liu
Mao-xiang
MX
Zhu
Jian-ping
JP
Xie
D000171:Acrolein / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D009841:Oligonucleotides
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D009153:Mutagens; D009841:Oligonucleotides; C488128:alpha-hydroxypropanodeoxyguanosine; D000171:Acrolein; D004247:DNA; D003849:Deoxyguanosine