Early morphologic alterations in mouse skin after topical application of 3-methylcholanthrene and its metabolites.
The effects of topical administration of 3-methylcholanthrene (MCA) or its metabolites on BALB/cKi mice were reported on inflammatory skin reactions, the alterations in epidermal thickness, the number of nucleated cells, pyknotic nuclei and/or nuclear fragments, and mitotic figures in the interfollicular epidermis (IFE). In the two-stage carcinogenesis system, MCA, the powerful complete carcinogen, induced an ordered sequence of cell changes strikingly similar to those caused by tumor-promoting agents such as the phorbol esters. These changes were absent after application of the "K-region" oxide of MCA. Other MCA metabolites also failed to induce notable inflammation, epidermal hyperplasia, and/or hypertrophy. Several MCA derivatives, however, caused a thinning of IFE paralleled by an increase in the relative number of pyknotic nuclei and a decrease in the total number of epithelial cells. The inhibitor of polycyclic hydrocarbon metabolism alpha-naphthoflavone did not prevent MCA-mediated skin reactions but, under suitable conditions, apparently potentiated the hyperplastic effects of MCA. The findings indicate that important events in the promotion phase of MCA-mediated skin carcinogenesis might be associated with the parent compound rather than with one of its metabolites.
D000287:Administration, Topical; D000818:Animals; D002467:Cell Nucleus / Q000473:pathology; D003877:Dermatitis, Contact; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D006965:Hyperplasia / Q000139:chemically induced; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000008:administration & dosage / Q000031:analogs & derivatives; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D005419:Flavonoids; D008748:Methylcholanthrene