harmine and Papilloma

Dibenzofluoranthene-12,13-dihydrodiol (DBF-12,13-DHD) is six times more mutagenic in Salmonella TA100 than dibenzofluoranthene-3,4-dihydrodiol (DBF-3,4-DHD). However, these two major dibenzo[a,e]fluoranthene (DBF) proximate metabolites, which are immediate precursors of the corresponding diolepoxides, showed on an equimolar 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 number 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 induction of tumours by DBF-3,4-DHD and DBF. The relationship between in vitro mutagenic activity in Salmonella and the carcinogenicity of DBF metabolites in mice appears to be qualitative rather than quantitative.

Topics: Alkaloids; Animals; Carbolines; Carcinogens; Carcinoma; Female; Fluorenes; Harmine; Mice; Mice, Inbred Strains; Mutagenicity Tests; Mutagens; Mutation; Papilloma; Salmonella typhimurium; Skin Neoplasms; Structure-Activity Relationship

The carcinogenic effects of aniline and norharman given alone or in combination were examined in rats. Neoplastic changes including hyperplastic changes of the urinary bladder were not found in all groups. Papillomas of forestomach were observed in 5 rats out of 110 rats. However, this was not significantly different among the groups. Pyelonephritis or chronic nephritis were also seen in all groups. Hematological and blood biochemical analysis did not show any notable difference in the animals treated with aniline and/or norharman.

Topics: Alkaloids; Aniline Compounds; Animals; Carbolines; Carcinogens; Harmine; Kidney Diseases; Male; Papilloma; Pituitary Neoplasms; Rats; Stomach Neoplasms; Urinary Bladder Neoplasms