Excision of hydrocarbon-DNA adducts and consequent cell survival in normal and repair defective human cells.
Survival curves for normal human cells and xeroderma pigmentosum variant cells (XP4BE) after ultraviolet radiation were indistinguishable. In comparison, cells from xeroderma pigmentosum complementation group A (XP12BE) were very sensitive to ultraviolet radiation. Complementation group C (XP2BE) cells were almost as sensitive as group A cells. These survival phenomena parallel to known unscheduled DNA synthesis responses of these cells to ultraviolet radiation, which, compared with normal cells, are: XP4BE, 100%; XP2BE, 20%; XP12BE, 2%. The relative capacities of these cells to excise 7-bromomethylbenz[a]anthracene-DNA adducts and to survive treatment with the carcinogen were similar to the responses to ultraviolet irradiation, except that the XP2BE cell line both excised and survived this damage far better than anticipated from its response to ultraviolet irradiation. Moreover, whilst in the normal cells and variant cells the ratio of hydrocarbon-adenine adduct to hydrocarbon-guanine adduct remaining in DNA decreased notably with excision, this ratio did not change significantly with excision in the XP2BE cell line. The relationship between greater excision capacity and increased cell survival in the experiments with the chemical carcinogen indicates that the unexcised damage is responsible for the cell-killing action of this agent. The different relative repair and survival responses of these cell lines to ultraviolet irradiation on the one hand, and to 7-bromomethylbenz[a]anthracene chemical carcinogen treatment on the other, indicate that in at least one of these cell lines (XP2BE), and possibly in all the lines, different cellular mechanisms are involved in the repair of DNA damage resulting from ultraviolet irradiation and that resulting from the chemical carcinogen treatment.
D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism*
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D004247:DNA