RATIONALE FOR SELECTING EXFOLIATED BLADDER CELL MICRONUCLEI AS POTENTIAL BIOMARKERS FOR ARSENIC GENOTOXICITY

Biomarkers of effect have important potential in epidemiology, since t hey may enable ascertainment of exposure-effect associations in relati vely inexpensive cross-sectional studies, with confirmation by short f ollow-up after cessation of exposure. Arsenic is known to cause human skin and lung cancer, and may also cause various internal cancers incl uding 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 relati ve risks for bladder cancer well above any other known environmental c arcinogen. Populations at increased risk for bladder cancer from other exposures, such as smoking and schistosomiasis infection, have elevat ed frequencies of micronuclei in exfoliated bladder cells. We have the refore proposed that the bladder cell micronucleus assay could be an a ppropriate 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 biomark er in currently exposed populations.