Dibenz[a,h]anthracene-induced subcutaneous tumors in mice. Strain sensitivity and the role of carcinogen metabolism.

Abstract

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.

• Authors: R A Lubet, G M Connolly, D W Nebert, R E Kouri
• Journal: Carcinogenesis (Carcinogenesis) Vol. 4 Issue 5 Pg. 513-7 ( 1983) ISSN: 0143-3334 [Print] England
• PMID: 6850980 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benz(a)Anthracenes
• Carcinogens
• Aryl Hydrocarbon Hydroxylases
• 1,2,5,6-dibenzanthracene

Topics

• Animals
• Aryl Hydrocarbon Hydroxylases (metabolism)
• Benz(a)Anthracenes (metabolism, toxicity)
• Carcinogens (metabolism)
• Male
• Mice
• Mice, Inbred Strains
• Microsomes, Liver (metabolism)
• Neoplasms, Experimental (chemically induced)
• Species Specificity