7,12-Dimethylbenz[a]anthracene plus near-u.v. light initiates DNA damage and repair in Chinese hamster cells.
Earlier results on the photodynamic action of several carcinogenic polycyclic aromatic hydrocarbons, and particularly 7,12-dimethylbenz[a]anthracene (DMBA), have been extended to determine if DMBA + near-u.v. light produces damage to DNA. DMBA by itself (30 min, approximately 24 degrees C) introduces relatively few breaks into genomic DNA. The addition of near-u.v. light, however, inserts large numbers of single-strand breaks in a dose-dependent way. Incubation following exposure initially results in the rapid repair of these breaks. A primary role for DNA damage in photodynamic cell killing is not supported by other observations, however. First, caffeine, an inhibitor of radiation-associated DNA repair processes, has only a minor effect on the oxygen-dependent killing of cells exposed to DMBA + u.v. light. Second, along with the repair of DNA breaks, the insertion of additional breaks becomes evident leading to a massive breakdown of genomic DNA due to an endonucleolytic-like attack. And third, lethally affected cells rapidly lose their surface attachment. Because light induces damage in DNA when DMBA is present, it is likely that DMBA becomes closely associated with DNA. Thus, a starting point for mutagenic and carcinogenic action in the absence of light is suggested although activation of DMBA by a P-450 system does not appear to be a prerequisite of DMBA-DNA association. Still, DNA as such may not be the initial or the primary target for light-induced cell killing. In addition to interacting with DNA, DMBA is sequestered by membranes, suggesting that killing results from an oxygen-dependent release of catabolic enzymes. These enzymes, which may come from lysosomes, degrade DNA but concomitantly release surface-attached cells into the medium.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D010777:Photochemistry; D014466:Ultraviolet Rays
D004277:DNA, Single-Stranded; D002110:Caffeine; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA