Protection by 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) against mammary tumors and leukemia during prolonged feeding of 7,12-dimethylbenz(a)anthracene to female rats.
Female Sprague-Dawley rats, 36 days old, were pretreated for 2 weeks either with 100 ppm 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) or 250 ppm S-(1,2-dicarbeth-oxyethyl)OO-dimethyldithiophosphate (Malathion) in the diet. From day 50 they were given, via stomach tube, 21 consecutive daily doses of 0.714 mg 7,12-dimethylbenz[a]anthracene (DMBA). Pesticide diets and observation of the animals for mammary tumors continued until necropsy, 230 days after the start of DMBA administration. DDT-treated rats had a significantly lower mammary tumor incidence, prolonged tumor latency period, and fewer tumors per rat than did the control group. Animals given Malathion (an organophosphate pesticide) had a higher mammary tumor incidence, shortened latency period, more tumors per rat, and more actively growing tumors than did the control group (DMBA only). Leukemia incidence in rats surviving to necropsy (230 days after the start of DMBA administration) was 11/20 for control, 2/29 for DDT, and 8/12 for Malathion-treated rats. Leukemia was primarily myelogenous. DDT may inhibit DMBA-induced mammary tumors and leukemia by stimulating hepatic metabolism and excretion of DMBA so that less carcinogen is available to peripheral tissues. Malathion may potentiate DMBA induction of mammary tumors and leukemia by inhibiting the same enzyme systems induced by DDT.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000037:antagonists & inhibitors*; D003634:DDT / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D007942:Leukemia, Experimental / Q000139:chemically induced*; D007951:Leukemia, Myeloid / Q000139:chemically induced; D008294:Malathion / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats
D001551:Benz(a)Anthracenes; D015127:9,10-Dimethyl-1,2-benzanthracene; D003634:DDT; D008294:Malathion