Rationale for selecting exfoliated bladder cell micronuclei as potential biomarkers for arsenic genotoxicity

Abstract

Biomarkers of effect have important potential in epidemiology, since they may enable ascertainment of exposure-effect associations in relatively inexpensive cross-sectional studies, with confirmation by short follow-up after cessation of exposure. Arsenic is known to cause human skin and lung cancer, and may also cause various internal cancers including bladder, kidney, and liver cancer. The strongest epidemiological association between arsenic ingestion and an internal cancer is that with bladder cancer. Epidemiological studies of a Taiwanese population exposed to high levels of arsenic from drinking water reported relative risks for bladder cancer well above any other known environmental carcinogen. Populations at increased risk for bladder cancer from other exposures, such as smoking and schistosomiasis infection, have elevated frequencies of micronuclei in exfoliated bladder cells. We have therefore proposed that the bladder cell micronucleus assay could be an appropriate biological marker of genotoxic effect of arsenic exposure. In this paper, we present the rationale for choosing the bladder cell micronucleus assay as a potential biomarker of effect for arsenic. We also briefly describe the studies we are conducting using this biomarker in currently exposed populations.