OCCUPATIONAL APPLICATIONS OF A HUMAN CANCER-RESEARCH MODEL

Many bladder cancers are indolent, and since there are no biomarkers t o predict progression, the prognosis is problematic. Utilizing an in v itro/in vivo human uroepithelial cell (SV-HUC.PC) transformation syste m, we investigated several molecular events occurring along the contin uum of exposure to disease outcome as potential biomarkers for occupat ional carcinogenesis, The model also served to generate information on the occupational carcinogenicity of N-hydroxy-4,4'-methylene bis(2-ch loroaniline) [N-OH-MOCA]. Two of 14 groups of SV-HUC.PC treated with v arious concentrations of N-OH-MOCA formed carcinomas in athymic nude m ice. Each of the biomarkers investigated demonstrated potential for in terventions/prevention applications of occupational bladder cancers bu t will require validation and further evaluation. Those investigated d isplaying potential occupational utility included the induction of orn ithine decarboxylase (ODC), DNA adducts, and altered proteins, as dete cted on HUC two-dimensional polyamylamide gel electrophoresis protein maps.