Chemistry and biology of DNA damage by malondialdehyde.
Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis which is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is a pyrimidopurinone called pyrimido[1,2-a]purin-10(3H)-one (M1G). Studies of site-specific mutagenesis indicate that M1G is mutagenic in bacteria and is repaired by the nucleotide excision repair pathway. M1G has been detected in liver, leukocytes, pancreas and breast from healthy human beings at levels ranging from 1 to 120 per 10(8) nucleotides. Several assays for M1G have been described which are based on mass spectrometry, 32P-postlabelling or immunochemical techniques. M1G appears to be a major endogenous DNA adduct in human beings that may contribute significantly to cancer linked to lifestyle and dietary factors. Recent advances in the chemistry and biology of M1G are reviewed.
Marnett
L J
LJ
A.B. Hancock Jr Memorial Laboratory for Cancer Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
D001940:Breast / Q000378:metabolism; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D004249:DNA Damage; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde / Q000737:chemistry / Q000633:toxicity*; D013058:Mass Spectrometry; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D009369:Neoplasms / Q000209:etiology; D010179:Pancreas / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D008315:Malondialdehyde