Groups of T.O. mice (Theiler's Original, derived from Swiss albino mice) were treated topically, with a single dose of 1.0 mg of 4CMB, 4HMB, or BC, or with 0.4 mg benzo[a]pyrene (B[a]P). Twice-weekly promotion of the treated skin area with croton oil was begun 1 week later. At 10 months the skin-tumour incidence in the positive control (B[a]P) was 8/19, with a mean latent period of 20 weeks. Both 4CMB and 4HMB have so far produced 1 papilloma each (1/36 at 40 weeks, and 1/39 at 34 weeks, respectively), while BC has produced none. Further time is required in order to ascertain whether these single papillomas will develop into carcinomas and thereby herald weak initiating activity for 4CMB and 4HMB.

Animals↗

PubMedDate not supplied

The UKEMS genotoxicity trial. A summary of the assays for skin tumour induction in mice, the subcutaneous implant test and the sebaceous gland suppression test.

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9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Induction of the P-450 I family of proteins by polycyclic aromatic hydrocarbons: possible relationship to their carcinogenicity.

The hypothesis has been put forward that mutagenic polycyclic aromatic hydrocarbons which induce the P-450 I family of cytochromes, the major enzyme system responsible for their activation, are likely to be carcinogenic. In order to test this hypothesis, rats have been pretreated with a number of polycyclic aromatic hydrocarbons of different mutagenic and carcinogenic potency and hepatic P-450 I activity was monitored using chemical probes such as the O-deethylation of ethoxyresorufin and metabolic activation of Glu-P-1 to mutagens, and immunologically employing polyclonal antibodies against purified rat P-450 I A1. All compounds studied enhanced P-450 I activity and induced P-450 I apoproteins but the extent of induction was very markedly different. The results are discussed with reference to the mutagenicity of these chemicals in the Ames test and their carcinogenicity in the classical mouse skin model. A relationship appears to exist between carcinogenicity of polycyclic aromatic hydrocarbons and their ability to induce hepatic P-450 I activity.

Animals↗