title: Extent of skin tumour initiation in mice by 7,12-dimethylbenz[alpha]anthracene and induction of arylhydrocarbon monooxygenase are not causally related.
abstract: In order to clarify further the relation between extent of arylhydrocarbon monooxygenase (AHM) induction and tumour initiation by polycyclic aromatic hydrocarbons, AHM activity and concentration of 7,12-dimethyl-benz[alpha]anthracene (DMBA) equivalents in dorsal epidermis were determined after both intragastric and topical administration of DMBA. Although in each case the dose applied caused comparable tumor incidences, both the extent of AHM induction and the concentration of DMBA equivalents were remarkably different: while topically applied DMBA stimulated AHM several-fold, intragastric instillation led to only a slight increase, if any. The concentration of DMBA equivalents in epidermis was about 100-fold higher after topical DMBA application than after intragastric administration. These data provide further evidence that extent of tumour initiation by DMBA and of AHM induction are not causally related; positive correlations found in certain cases appear to be fortuitous. Induction of AHM seems to be rather a function of DMBA concentration adjustment in epidermis and to indicate, if anything, elevated detoxification.
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage / Q000633:toxicity*; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced*
chemical_list: D000873:Anthracenes; D001189:Aryl Hydrocarbon Hydroxylases