PRIMARY AROMATIC AMINES THAT WERE IMPLICATED IN BLADDER CARCINOGENESIS (BASED ON THE EPIDEMIOLOGICAL DATA WITH WORKERS IN RUBBER AND DYE INDUSTRIES) EXHIBIT SEX AND SPECIES SPECIFICITY.

PRIMARY AROMATIC AMINES THAT WERE IMPLICATED IN BLADDER CARCINOGENESIS (BASED ON THE EPIDEMIOLOGICAL DATA WITH WORKERS IN RUBBER AND DYE INDUSTRIES) EXHIBIT SEX AND SPECIES SPECIFICITY. URINARY AND BLADDER CANCER IS MORE PREVALENT IN CAUCASIAN MALES. AROMATIC AMINES ARE MORE CARCINOGENIC IN DOGS AND LESS ACTIVE IN RODENTS, WHICH CORRELATES TO THE RELATIVE METABOLIC ACTIVITIES IN RESPECTIVE TISSUES. RESPONSE OF INDIVIDUALS TO CARCINOGENICITY RISK DEPENDS ON GENETIC HETEROGENEITY OF DRUG METABOLIZING CAPABILITY, WHICH IN TURN IS CONTROLLED BY SECONDARY FACTORS SUCH AS AGE, SEX, FOOD HABITS, SOCIAL AND ENVIRONMENTAL THE PROPOSED RESEARCH WILL DEVELOP CELL-MEDIATED METABOLISM/MUTAGENESIS STUDIES TO EXAMINE CELL/TISSUE/SPECIES SPECIFICITIES FOR A NUMBER OF BLADDER CARCINOGENS. SEVERAL FACTORS THAT AFFECT INDUCTION AND PROMOTION OF BLADDER CARCINOGENESIS WILL BE INVESTIGATED DURING PHASE II OF THIS PROJECT. THREE AROMATIC AMINES (2-ACETYLAMINOFLUORENE, 2-NAPHTHYLAMINE, BENZIDINE AND TWO NITROSAMINES (NITROSODIETHANOLAMINE, NITROSODIPHENYLAMINE) WILL BE TESTED WITH RAT, HAMSTER, PIG, DOG, BABOON, BOVINE, AND HUMAN UROTHELIAL CELLS AND COMPARED TO THE ACTIVITY OF HEPATOCYTES. ACTIVITY WILL BE MEASURED WITH THE SALMONELLA ASSAY IN PHASE I AND WITH CHO-MUTAGENESIS, CYTOGENETIC ASSAYS, AND UNSCHEDULED DNA SYNTHESIS WITH RAT HEPATOCYTES IN PHASE II. THE ROLES PLAYED BY THE FOLLOWING WILL BE EVALUATED IN PHASE A.CONVENTIONAL ENZYME INDUCERS, B.CYTOCHROME OXIDASE INHIBITORS, C.TUMOR PROMOTING AGENTS, D.DIETARY CONSTITUENTS, E.HORMONES, F.RESIDENT BACTERIAL FLORA, AND