Additivity of cytotoxic damage due to dimethylbenz(a)anthracene and X rays.
7,12-Dimethylbenz(a)anthracene is one of a group of polycyclic aromatic hydrocarbons that are known to be indirectly acting carcinogens. As a product of the incomplete combustion of complex hydrocarbons, dimethylbenzanthracene is present in the environment and may therefore act on living systems in conjunction with ionizing radiation. We have studied the cytotoxic effects of dimethylbenzanthracene by itself, together with other polycyclic aromatic hydrocarbons, and combined with X radiation. Pre- or postirradiation treatment of mouse C3H 10T1/2 cells with dimethylbenzanthracene progressively removes the shoulder of the X-ray survival curve and, consistent with that observation, the survival sparing from dose fractionation is progressively lost. The cotreatment of cells with 3-methylcholanthrene and dimethylbenzanthracene largely abrogates the killing due to the latter compound alone and, accordingly, returns the shoulder to the survival curve. The application of dimethylbenzanthracene, or similar compounds, between X-ray dose fractions, separated by 4 h, is without effect quite likely because of the need for metabolic activation of the compound for effectiveness. Dimethylbenzanthracene is believed to be genotoxic because, after it is activated, it forms bulky adducts with DNA. Hence these results suggest that bulky adducts are a form of DNA damage operationally equivalent to sublethal X-ray damage.
Chen
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Department of Radiology and Radiation Biology, Colorado State University, Fort Collins 80523.
Wells
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Elkind
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D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D003043:Cocarcinogenesis; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H
D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene