title: Repair of ultraviolet damage in human cells also exposed to agents that cause strand breaks, crosslinks, monoadducts and alkylations.
abstract: Excision repair of UV damage in human cells was measured by the incorporation of new bases into DNA after exposure to UV light and variety of other carcinogens including X-rays, furocoumarins plus 360 nm light (8-methoxypsoralen (8-MOP), 4'-aminomethyl 4,5',8-trimethylpsoralen hydrochloride (AMT) and angelicin), methyl methanesulfonate (MMS), dimethyl sulfate (DMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Repair of UV damage was unaffected by concomitant exposure to X-rays. Furocoumarin adducts and alkylating agents, however, interacted with UV repair and reduced the amount of repair replication observed. The interaction between repair of furocoumarin and UV damage is consistent with the involvement of a common DNA repair pathway: its saturation with respect to repair of UV damage also results in saturation with respect to other lesions involving that pathway. The observed effect of alkylating agents on UV repair, however, cannot be due to saturation of a common pathway because damage from these agents are repaired by different mechanisms than UV damage. Instead, it appears likely that the effect is due to alkylation damage to repair enzymes. From a consideration of the degree of protein alkylation at millimolar concentrations of alkylating agents, we estimate that the UV repair system could consist of an extremely large complex of protein subunits in the order of 1 million molecular weight. Whereas some previous studies have used concomitant exposures to pair of different agents to determine whether the damage they produce is repaired by common or independent pathways, our results indicate that such a method is an unreliable indicator of the number of repair pathways.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D014466:Ultraviolet Rays; D014965:X-Rays
chemical_list: D000477:Alkylating Agents; D002273:Carcinogens; D003432:Cross-Linking Reagents; D011564:Furocoumarins