Molecular biological studies on environmental chemical pollutants interfering with endocrine systems

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We studied an endocrine disruptor, cadmium, by molecular biological methods. Our project included two studies : gene expression induced by cadmium exposure and genetic analyses of Itai-itai disease which is caused by chronic exposure to cadmium.[Gene expression induced by cadmium exposure] To clarify the effects of cadmium on the endocrine system, we firstly screen the genes responsive to cadmium in COS-7 cells with a subtractive suppressive hybridization (SSH) method. We have detected more than 100 mRNA species which were induced by cadmium exposure, and identified their origins by sequencing analysis. The genes responsive to cadmium were as follows : metallothionein II, zeta-crystalline, cytochrome C oxidase subunit IV, glutathione synthetase, serine/threonine protein kinase, heat shock protein 10, transduction beta-I subunit, tunp, lipocortin II hsp 10, hsp 40, hsp 60, hsp 86, BAG-3, complement cytolysis inhibitor (CLI) and so on. Each of them showed its characteristic expression pattern when cadmium concentration and exposure time changed. Further analyses are required to clarify the relationships between the genes responsive to cadmium and the endocrine system.[Genetic analyses of itai-itai disease] In order to clarify the role of estrogen receptor α on the pathogenesis of itai-itai disease, we examined the genotypic polymorphisms in estrogen receptor α gene of the patients with itai-itai disease and compared them with those of control subjects. We examined PuvII, XbaI RFLP polymorphism in intron 1 and AT repeat polymorphism in upstream region of the estrogen receptor α gene. The genotypic distributions of the patient group were similar to those of the control groups, hence no itai-itai disease-related pattern of genotypic distribution was observed. We conclude that polymorphisms of the gene may not be associated with itai-itai disease.