Rodent bladder tumors do not always predict for humans.
Dr. David Clayson, 20 years ago, suggested that chemicals which lead to the formation of calculi in rodents might pose an artifact with respect to extrapolation to potential carcinogenic risk to humans. We reviewed what has been learned about the role of calculi in urinary bladder carcinogenesis in the ensuing 20 years, along with several examples. Formation of microcrystalluria and amorphous precipitate also poses problems in interpretation and examples are described. The chemicals producing these solid urinary materials are non-genotoxic, with marked increase in cell proliferation being the mode of action by which they are able to produce cancer in long-term rodent bioassays.
Cohen
S M
SM
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Lawson
T A
TA
D000818:Animals; D016477:Artifacts; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D011237:Predictive Value of Tests; D051381:Rats; D015203:Reproducibility of Results; D018570:Risk Assessment; D012377:Rodentia; D001744:Urinary Bladder Calculi / Q000139:chemically induced* / Q000150:complications / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000652:urine
D002273:Carcinogens