The distribution of DMBA and its dihydrodiols in tissues of control and Sudan-III-treated Long-Evans rats after the injection (i.v.) in vivo of a leukaemogenic dose of the hydrocarbon.
7,12-Dimethylbenz[a]anthracene (DMBA) is a potent leukaemogenic agent in Long-Evans rats when it is administered i.v. in vivo. The prior oral administration of Sudan III [1(p-phenylazo-phenylazo)-2-naphthol] protects animals from the leukaemogenic effects of this compound. Sudan-III-treatment resulted in an increased rate of removal of DMBA from the livers and blood of treated animals and resulted in a reduced level of accumulation of the hydrocarbon in its presumed target tissue, the bone marrow. The regio-selective hepatic metabolism of DMBA was altered in Sudan-III-treated animals, thus only trans-3,4-dihydro-3,4-dihydroxy-DMBA was recovered from the livers of control animals whereas only trans-8,9-dihydro-8,9-dihydroxy-DMBA was recovered from the livers of Sudan-III-treated animals. The distribution of DMBA dihydrodiols in the blood and in the bone marrow was found to reflect the findings in the liver. DMBA, when incubated with rat bone marrow cells in vitro, was metabolized to probable phenolic compounds but no evidence whatsoever was found for dihydrodiol formation in these cells. Taken together these results are consistent with a model in which Sudan-III-induced alterations in the regio-selective hepatic metabolism of DMBA are responsible for the protection against leukaemogenesis afforded by the administration of that compound. The probable mechanism of protection is the induction in liver of a cytochrome P450, probably P450c.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D001853:Bone Marrow / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D007942:Leukemia, Experimental / Q000139:chemically induced*; D008099:Liver / Q000378:metabolism; D051381:Rats
D001391:Azo Compounds; C013956:7,12-dimethylbenz(a)anthracene-dihydrodiol; D015127:9,10-Dimethyl-1,2-benzanthracene; C033006:sudan III