Occupational applications of a human cancer research model.
Many bladder cancers are indolent, and since there are no biomarkers to predict progression, the prognosis is problematic. Utilizing an in vitro/in vivo human uroepithelial cell (SV-HUC.PC) transformation system, we investigated several molecular events occurring along the continuum of exposure to disease outcome as potential biomarkers for occupational carcinogenesis. The model also served to generate information on the occupational carcinogenicity of N-hydroxy-4,4'-methylene bis(2-chloroaniline) [N-OH-MOCA]. Two of 14 groups of SV-HUC.PC treated with various concentrations of N-OH-MOCA formed carcinomas in athymic nude mice. Each of the biomarkers investigated demonstrated potential for interventions/prevention applications of occupational bladder cancers but will require validation and further evaluation. Those investigated displaying potential occupational utility included the induction of ornithine decarboxylase (ODC), DNA adducts, and altered proteins, as detected on HUC two-dimensional polyacrylamide gel electrophoresis protein maps.
Savage
R E
RE
Biochemical Toxicology Section, National Institute for Occupational Safety and Health, Cincinnati, OH 45226, USA.
DeBord
D G
DG
Swaminathan
S
S
Butler
M A
MA
Snawder
J
J
Kanitz
M H
MH
Cheever
K
K
Reid
T
T
Werren
D
D
D000818:Animals; D015415:Biomarkers; D002273:Carcinogens / Q000633:toxicity*; D006801:Humans; D008753:Methylenebis(chloroaniline) / Q000031:analogs & derivatives / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009784:Occupational Diseases / Q000139:chemically induced* / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000378:metabolism*
D015415:Biomarkers; D002273:Carcinogens; D008753:Methylenebis(chloroaniline)