Biomarkers of exposure, effects and susceptibility in humans and their application in studies of interactions among metals in China

Biomonitoring employs three categories of biomarkers: Biomarkers of exposure, i.e. measurements of metal concentrations in a compartment in the body reflecting external or internal exposure; Biomarkers of effects include early as well as clinical effects. Biomarkers of susceptibility indicate individuals with increased sensitivity of target molecules or metabolism causing increased target dose.The three categories of biomarkers were used in studies of health effects of metal exposures in China. Adverse effects on the kidney tubules with increased levels of the effect biomarkers beta-2-microglobulin in urine (UB2M) and urinary N-acetyl-beta-d-glucosaminidase (UNAG) were found among Cd exposed population groups in China. Among persons exposed to Cd, occupationally or in the general environment, the level of Cd-induced metallothionein mRNA (MTmRNA) in peripheral lymphocytes appeared as a useful indicator of the ability of individuals to synthesize MT. Persons with low MTmRNA levels displayed higher biomarker values of renal tubular damage than persons with high levels of MTmRNA, at comparable levels of urinary Cd. Other studies demonstrated the importance of auto-antibodies against metallothionein in plasma (MTab) in modifying the response to Cd. Persons with high levels of MTab displayed tubular proteinuria at lower levels of urinary Cd than persons with low levels of MTab. Studies in two metal contaminated areas in China demonstrated clear interactions between Cd and inorganic arsenic. Combined exposure, with increased levels of As and Cd in urine, caused considerably higher biomarker values of renal tubular damage, measured as increased urinary levels of B2M or NAG, than each of the exposures alone.