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© 1987 Oxford University Press

research-article

Marked differences between mutagenicity in Salmonella and tumour-initiating activities of dibenzo[a,e] fluoranthene proximate metabolites; initiation inhibiting activity of norharman

François Zajdela 1, Odette Perin-Roussel and Saad Saguem

Unité de Recherche sur les Facteurs de Régulation de la Prolifération Cellulaire et la Cancérogénèse (U.22), Institut Curie Bât. 110, Centre Universitaire, 91405 Orsay Cedex, France

1To whom reprint requests should be sent

Dibenzofluoranthene-12,13-dihydrodiol (DBF-12,13-DHD) is six times more mutagenic in Salmonella TA100 than diben-zofluoranthene-3,4-dihydrodiol (DBF-3,4-DHD). However, these two major dibenzo[a,e]fluoranthene (DBE) proximate metabolites, which are immediate precursors of the corre-sponding diolepoxides, showed on an equiinolar basis nearly identical initiation activities on mouse skin; they induced three times more papillomas than the parent hydrocarbon. On the other hand the epithelioma initiation capacities, i.e. the num-ber of papillomas progressing to malignant tumours, of DBF or the two dibenzofluoranthene dihydrodiols were equivalent. Norharman, a putative vicinal diolepoxidation inhibitor in DBF metabolism when administered topically together with the initiation dose (100 nmol), strongly inhibited the induc-tion of tumours by DBF-3,4-DHD and DBF. The relationship between Dibenzofluoranthene-12,13-dihydrodiol (DBF-12,13-DHD) is six times more mutagenic in Salmonella TA100 than diben zofluoranthene-3,4-dihydrodiol (DBF-3,4-DHD). However, these two major dibenzo (DBE) proximate metabolites, which are immediate precursors of the corre sponding diolepoxides, showed on an equiinolar basis nearly identical initiation activities on mouse skin; they induced three times more papillomas than the parent hydrocarbon. On the other hand the epithelioma initiation capacities, i.e. the num ber of papillomas progressing to malignant tumours, of DBF or the two dibenzofluoranthene dihydrodiols were equivalent. Norharman, a putative vicinal diolepoxidation inhibitor in DBF metabolism when administered topically together with the initiation dose (100 ninol), strongly inhibited the induc tion of tumours by DBF-3,4-DHD and DBF. The relationship between in vitro mutagemc activity in Salmonella and the carcinogenicity of DBF metabolites in mice appears to be qualitative rather than quantitative.in vitro mutagemc activity in Salmonella and the carcinogenicity of DBF metabolites in mice appears to be qualitative rather than quantitative.


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