Dibenz[a,h]anthracene-induced subcutaneous tumors in mice. Strain sensitivity and the role of carcinogen metabolism.
Four inbred strains of mice (C3H/HeJ, C57BL/6J, AKR/J, and DBA/2J) were injected s.c. with 150 micrograms of dibenz[a,h]anthracene and followed for 9 months. Strains C3H/HeJ and C57BL/6J were most susceptible to dibenz[a,h]anthracene-induced carcinogenesis with 80% and 53% incidence of tumors, respectively. Strains AKR/J and DBA/2J were much less sensitive with only one tumor observed out of a total of 60 treated mice. Dibenz[a,h]anthracene was shown to induce hepatic aryl hydrocarbon hydroxylase activity in the two sensitive strains, C3H/HeJ and C57BL/6J, but not in the two resistant strains, AKR/J and DBA/2J. When 3-methylcholanthrene-treated liver microsomes from the four strains were studied for dibenz[a,h]anthracene metabolism in vitro, the two sensitive strains not only demonstrated a 3- to 4-fold greater overall rate of metabolism than the two resistant strains, but also showed a quantitative shift with a greater percentage of the total metabolites being the 3,4-diol of dibenz[a,h]anthracene. This diol is the presumed precursor to the apparent ultimate carcinogen, dibenz[a,h]anthracene 3,4-diol-1,2-epoxide.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D013045:Species Specificity
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D001189:Aryl Hydrocarbon Hydroxylases; C026486:1,2,5,6-dibenzanthracene