Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts: involvement of two excision repair mechanisms in vitro.
Polycyclic aromatic hydrocarbons (PAHs) are significant environmental pollutants representing an important risk factor in human cancers. DNA adducts formed by the ultimate carcinogens of PAHs are potentially toxic, mutagenic and carcinogenic. DNA repair represents an important defense system against these genotoxic insults. Using a human cell-free system we have examined repair of DNA lesions induced by several PAH dihydrodiol epoxides, including anti-(+/-)-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide, anti-(+/-)-benz[a]anthracene-trans-3,4-dihydrodiol-1,2-epoxide, anti-(+/-)-benz[a]anthracene-trans-8,9-dihydrodiol-10,11-epoxide, anti-(+/-)-benzo[b]fluoranthene-trans-9,10-dihydrodiol-11,12-epoxide and anti-(+/-)-chrysene-trans-1,2-dihydrodiol-3,4-epoxide. Effective repair of DNA damage induced by these five PAH metabolites was detected. Two distinct mechanisms of excision repair were observed. The major repair mechanism is nucleotide excision repair (NER). The other mechanism is independent of NER and correlated with the presence of apurinic/apyrimidinic sites in the damaged DNA, thus presumably reflecting base excision repair (BER). However, the contribution of BER to different PAH lesions varied in vitro. These results suggest the possibility that BER may also play an important role in repair of certain PAH-induced DNA lesions.
Graduate Center for Toxicology, University of Kentucky, Lexington 40536, USA.
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Braithwaite
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Wu
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Wang
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002474:Cell-Free System; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*
D002273:Carcinogens; D011084:Polycyclic Aromatic Hydrocarbons; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA