Mutagenicity of heavy metals

Severe chromosome aberrations have been observed in lymphocyte cultures from workers of the zinc industry. Such workers are however exposed simultaneously to several heavy metals which are in decreasing order of importance; zinc, lead and cadmium. In an attempt to elucidate the component responsible for the aberrations observed, the effects of zinc, lead and cadmium were studied separately, using various 'in vitro' and 'in vivo' methods. 'In vitro' studies: human lymphocytes were cultured for 48 or 72 h in the presence of each metal salt, at 3 subtoxic dose levels, which were added 0 and 24 h after initiation of the culture. Zinc but not lead and cadmium salts produced 'in vitro' severe chromosome abnormalities under these conditions. 'In vivo' studies: previously it was found that a calcium-deficient diet enhanced the yield of chromosome aberrations in cultured lymphocytes from lead-intoxicated monkeys. These different observations suggest that under normal 'in vitro' conditions, zinc is the principal agent responsible for producing chromosomal aberration but that in addition nutritional deficiencies particularly that of calcium and the interaction of heavy metals such as lead may participate in causing chromosome aberrations in the industrial workers. In order to investigate the respective roles of calcium deficiency and interaction with heavy metals, the chromosomal aberrations in bone marrow cells were studied in C57B1 mice given, from the age of two months for a period of one months, a normal diet or a calcium-deficient diet with and without addition of zinc, lead or cadmium. It appears from this last study that calcium deficiency is an important cofactor in heavy-metal mutagenesis and, under such nutritional factors, zinc as well as lead but not cadmium seem to be mutagenic. These metals can thus be responsible for the chromosomal aberrations found in some marginally nourished workers from the zinc industry.