Peripheral biomarkers and exposure to manganese

Biochemical mechanisms underlying manganese (Mn) toxicity include dopamine (DA) auto-oxidation and free radical generation with subsequent neuronal da mage. A neuroendocrine approach based on the measurement of serum prolactin (PRL) has been proposed to assess the tonic inhibition of pituitary lactot rope cells by the tubero-infundibular DA system. Low level exposure to Mn o xides in industrial settings is associated with a shift in the distribution of serum PRL towards higher levels as compared to matched controls. The fo llow-up of a small cohort of workers from a ferromanganese plant showed tha t the increased prevalence of abnormally high PRL values is stable over tim e. Although the mechanistic basis for their application is less straightfor ward, other biochemical markers such as dopamine beta-hydroxylase and monoa mine oxidase Type B, have also been assessed. Contrary to PRL levels, these markers cannot be recommended to monitor early biochemical effects of mang anese exposure at the workplace. Early biochemical events can be modified b y genetically determined individual differences. Owing to the possible role of a reduced capacity of glutathione conjugation as a risk factor increasi ng the susceptibility to the action of free radicals generated in the prese nce of Mn, the class mu glutathione S transferase (GSTM1) genotype has a Is o been assessed in workers occupationally exposed. However, the GSTM1 null genotype does not appear to play an important role in the susceptibility to biochemical effects of Mn. A logistic model of the dose-response relations hip based on urinary Mn as marker of exposure indicates that the benchmark dose corresponds to Mn levels as low as 0.4 mu g/l. This would imply that e nvironmental exposure to Mn may contribute to abnormally high serum PRL in the general population. (C) 1999 Inter Press, Inc.