Shunichiro Imamiya

A mechanism of cadmium poisoning: the cross effect of calcium and cadmium in the calmodulin-dependent system

The effects of the intraventricular (IVT) administration of cadmium on the amount of dopamine (DA) in various regions of the mice brain were analyzed immunohistochemically using a microphotometry system. DA levels in the neostriatum and nucleus accumbens were increased by approximately 30% (p<0.01) by the IVT administration of CdCl2 (1 μmol/kg). This effect was abolished by the calmodulin antagonist, W-7 (4.2 μg/mouse, IVT). The effects of cadmium on DA levels in the brain were very similar to those seen with calcium. Combining these results with our previous finding that calmodulin does not have the ability to distinguish between calcium and cadmium, a mechanism of cadmium poisoning is suggested in which cadmium activates catecholamine synthesizing enzyme and numerous other enzymes through calmodulin-dependent systems, thereby disturbing many functions in the organism.

Evidence on n -acetyltransferase Allele-associated Metabolism of Hydrazine in Japanese Workers

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Exposure to 2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) and Acute Liver Dysfunction: A Causal Inference

Exposure to 2,2‐Dichloro‐1,1,1‐trifluoroethane (HCFC‐123) and Acute Liver Dysfunction: A Causal Inference: Toru Takebayashi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Acute liver dysfunction has been reported among workers repeatedly exposed to 2,2‐dichloro‐1,1,1‐trifluoroethane (HCFC‐123), a substitute for trichlorofluoromethane. Causality between occupational exposure to HCFC‐123 and liver dysfunction was examined. Levels of exposure to HCFC‐123 were estimated retrospectively by reproducing working conditions and by a job record survey. Health surveillance, including liver function and subjective symptoms, was done when two workers first complained of ill health. The mean HCFC‐123 concentration in air was more than 200 ppm with a peak concentration of about 1,000 ppm in a processing area where HCFC‐123 was used. HCFC‐123 of 18‐24 ppm was detected in the adjunct areas where HCFC‐123 vapor was not generated. Workers (n=14) were then classified into high (n=5) and low (n=9) exposure groups according to the estimated exposure level, which was confirmed by determination of urinary trifluoroacetic acid. Mean serum AST and ALT levels were 236 IU//and 476 IU// among the high‐exposed workers, and exceeded 500 IU// in three workers. Various types of symptoms involving the central nervous system and digestive organs, and irritation of the mucous membrane, were also experienced. The degree and prevalence of these health effects were higher in the high exposure group, which indicates the exposure‐effect and exposure‐response relationships. The consistency and temporality of the relationship between HCFC‐123 exposure and the observed health effects were also confirmed. We conclude that repeated exposure to high concentrations of HCFC‐123 for no more than five weeks causes acute severe liver dysfunction with various symptoms in humans. Biological plausibility must be clarified to confirm the causality.

Metallothionein-like cadmium binding protein in rat testes administered with cadmium and selenium.

It is well known that the testicular damage caused by acute cadmium toxicity are protected by simultaneous selenium administration with cadmium, and that the cadmium concentration in the testis increases remarkably as compared with that of only cadmium administration. The increased cadmium in the testis was found in the high molecular weight fraction containing selenium, and it has been thought that the shift of cadmium from the low molecular weight fraction to the high molecular weight fraction containing selenium is an important protection mechanism. However, the cadmium concentration in this high molecular weight fraction decreased with time, then re-shifted to the fraction of metallothionein, a low molecular weight protein having a protective effect against cadmium toxicity. While recently studying the cadmium binding protein, like metallothionein, in testes, it has been reported that the amino acid composition of cadmium binding protein in testis is not similar to that of the hepatic metallothionein. The present study was undertaken to clarify the properties of the increased cadmium binding protein in the testis protected by simultaneous selenium administration with cadmium.