Formation and repair of furocoumarin adducts in alpha deoxyribonucleic acid and bulk deoxyribonucleic acid of monkey cells.
We have extended our previous finding that excision repair of furocoumarin photoadducts is deficient in the highly repetitive alpha DNA sequences in cultured African green monkey cells. The formation and removal from DNA of the individual photoadducts of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) were monitored by analysis of DNA hydrolysates using a high-pressure liquid chromatography procedure that separated the major adducts from each other and also resolved the two diastereomers of the most frequent monoadduct. The overall deficiency in removal of HMT adducts from alpha DNA was similar to that previously observed by us with 4'-(aminomethyl)-4,5',8-trimethylpsoralen and angelicin. The two diastereomers of the furan-T monoadducts were formed in the same relative amounts in alpha DNA and bulk DNA whether photoaddition was in vivo or in vitro, and they were removed from cellular DNA at the same relative rates. Therefore, the deficient removal of furocoumarin adducts from alpha cannot be due to preferential formation of some adduct inherently refractory to repair. However, in vivo, the photochemical conversion of the furan-T monoadducts to diadducts was markedly reduced in alpha DNA, relative to that in bulk DNA. This indicates a possible conformational constraint in the internucleosomal DNA in alpha-chromatin which may account for the deficiency in repair.
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification / Q000528:radiation effects; D004260:DNA Repair; D011564:Furocoumarins / Q000494:pharmacology*; D007700:Kinetics; D014307:Trioxsalen / Q000031:analogs & derivatives / Q000494:pharmacology*; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D011564:Furocoumarins; C016507:hydroxymethyltrioxsalen; D004247:DNA; D014307:Trioxsalen