Jump to main content
Jump to site search

Issue 4, 2018
Previous Article Next Article

Screening for human urinary bladder carcinogens: two-year bioassay is unnecessary

Author affiliations

Abstract

Screening for carcinogens in general, and for the urinary bladder specifically, traditionally involves a two-year bioassay in rodents, the results of which often do not have direct relevance to humans with respect to mode of action (MOA) and/or dose response. My proposal describes a multi-step short-term (90 day) screening process that characterizes known human urinary bladder carcinogens, and identifies those reported in rodent two-year bioassays. The initial step is screening for urothelial proliferation, by microscopy or by increased Ki-67 labeling index. If these are negative, the agent is not a urinary bladder carcinogen. If either of these is positive, an MOA and dose response analysis are performed. DNA reactivity is evaluated. If the chemical is non-DNA reactive, evaluation for cytotoxicity is performed. This involves examination of the urothelium and urine, the latter to identify the generation of urinary solids (e.g. calculi). If urinary solids are the cause of cytotoxicity, the MOA is not relevant to human cancer, but dose response becomes essential for evaluating potential toxicity to humans. If cytotoxicity occurs but no urinary solids are detected, urinary concentrations of the chemical and its metabolites are evaluated, and compared to in vitro cytotoxicity against rodent and human immortalized urothelial cell lines. Based on this process, a screen for urinary bladder carcinogenicity is reliable, and more importantly, can be based on MOA and dose response analyses useful in the overall risk assessment for possible human bladder cancer. The proposed procedure is shorter, less expensive and more relevant than the two-year bioassay.

Graphical abstract: Screening for human urinary bladder carcinogens: two-year bioassay is unnecessary

Back to tab navigation

Publication details

The article was received on 02 Nov 2017, accepted on 22 Jan 2018 and first published on 23 Jan 2018


Article type: Paper
DOI: 10.1039/C7TX00294G
Citation: Toxicol. Res., 2018,7, 565-575
  •   Request permissions

    Screening for human urinary bladder carcinogens: two-year bioassay is unnecessary

    S. M. Cohen, Toxicol. Res., 2018, 7, 565
    DOI: 10.1039/C7TX00294G

Search articles by author

Spotlight

Advertisements