The relationship between
arsenic exposure and DNA damage in patients with acute or chronic
arsenic poisoning was analyzed. Urinary
8-hydroxydeoxyguanine (8-OHdG) concentrations were measured as an indication of oxidative DNA damage. A remarkable increase in 8-OHdG in the urine was observed in 60% of 52 patients with acute
arsenic poisoning from the accidental oral intake of the
arsenic trioxide. This was two- to threefold higher than levels in normal healthy subjects (n = 248). There was a clear relationship between
arsenic concentrations in urine after acute
poisoning and elevated levels of 8-OHdG. Levels of urinary 8-OHdG returned to normal within 180 days after the acute
arsenic poisoning event. In patients chronically poisoned by the consumption of well water with elevated levels of
arsenate [As(V)], elevated 8-OHdG concentrations in urine were also observed. A significant correlation between the 8-OHdG levels and
arsenic levels in the urine was observed in 82 patients with chronic
poisoning. Thus, evidence of oxidative DNA damage occurred in acute
arsenic poisoning by
arsenite [As(III)] and in chronic
arsenic poisoning by As(V). In chronic
poisoning patients provided low-
arsenic drinking water, evidence of DNA damage subsided between 9 months and 1 year after the high levels of
arsenic intake were reduced. The initial level of
arsenic exposure appeared to dictate the length of this recovery period. These data indicate that some aspects of chronic and acute
arsenic poisoning may be reversible with the cessation of exposure. This knowledge may contribute to our understanding of the risk elevation from
arsenic carcinogenesis and perhaps be used in a prospective fashion to assess individual risk.