Differential DNA-protein crosslinking in lymphocytes and liver following chronic drinking water exposure of rats to potassium chromate

Abstract

Carcinogenic chromium (VI) compounds are persistent environmental contaminants with potential for human exposure through drinking water. One lesion associated with chromium (VI) exposure is the formation of DNA-protein crosslinks (DPC). In an attempt to develop markers of chromium exposure, the formation of DPC in lymphocytes was investigated. Fisher 344 rats were exposed to K2CrO4 in their drinking water for 3 and 6 weeks at concentrations of 100 and 200 ppm chromium. No DPC could be detected in isolated splenic lymphocytes using the alkaline elution technique or by using a polyclonal antibody to chromate-induced DPC. However, increased complexing of proteins with DNA was demonstrated in liver following 3 weeks of exposure at both 100 and 200 ppm chromium. Intraperitoneal administration of potassium chromate did not induce detectable DPC in lymphocytes; however, an increased association of proteins with isolated DNA was detected in the liver. DPC were also induced in isolated splenic lymphocytes following a 2-hr exposure in vitro to 100 microM K2CrO4 in a salts-glucose medium. Although chromium was detected in blood, liver, and kidney, blood levels were comparatively much lower. A comparison of chromium levels required to induce DPC in lymphocytes in vitro and the amount absorbed orally suggests that the white blood cell chromium levels following oral exposure may be too low to induce measurable DNA-protein crosslinks in lymphocytes.