de Paris P, Caroldi S
Istituto di Medicina del Lavoro, Università di Padova, Italy.
Biomed Environ Sci. 1995 Jun;8(2):114-21.
Serum dopamine-beta-hydroxylase (DBH) inhibition has been reported in lead workers treated with CaNa2EDTA and in alcoholic patients repeatedly treated with the alcohol aversive drug Disulfiram. The mechanism of inhibition involves Cu++ chelation at the active site of DBH. The effect of CaNa2EDTA and Disulfiram on serum DBH has been compared to the effect of dithiocarbamate pesticides in vitro for the possible use of serum DBH determination for the biological monitoring of workers exposed to these pesticides. Most dithiocarbamates inhibit human serum DBH at micromolar concentrations (range of I50, 0.027-1.6 mumol/L). The inhibitory potency increased from methyl- and dimethyl dithiocarbamates to diethyl dithiocarbamates up to the most potent ethylene bisdithiocarbamates. The I50 of CaNa2EDTA was 3.8 mumol/L, higher than those of dithiocarbamates. Copper addition to the test system reactivated at stoichiometric concentrations dithiocarbamate-inhibited DBH indicating that both base line values and percent of inhibition can be calculated in a single blood sample. Results suggest that serum DBH determination could be useful in case of acute poisoning involving high doses of dithiocarbamate pesticides.
据报道，接受CaNa2EDTA治疗的铅作业工人以及反复接受戒酒药物双硫仑治疗的酗酒患者体内的血清多巴胺-β-羟化酶（DBH）受到抑制。抑制机制涉及DBH活性位点处的Cu++螯合。已将CaNa2EDTA和双硫仑对血清DBH的影响与二硫代氨基甲酸盐类农药在体外的影响进行了比较，以探讨血清DBH测定用于对接触这些农药的工人进行生物监测的可能性。大多数二硫代氨基甲酸盐类在微摩尔浓度下（半数抑制浓度范围为0.027 - 1.6 μmol/L）会抑制人血清DBH。抑制效力从甲基和二甲基二硫代氨基甲酸盐类到二乙基二硫代氨基甲酸盐类逐渐增强，直至最强效的亚乙基双二硫代氨基甲酸盐类。CaNa2EDTA的半数抑制浓度为3.8 μmol/L，高于二硫代氨基甲酸盐类。向测试系统中添加铜可使化学计量浓度的二硫代氨基甲酸盐类抑制的DBH重新激活，这表明可以在单个血样中计算基线值和抑制百分比。结果表明，血清DBH测定对于涉及高剂量二硫代氨基甲酸盐类农药的急性中毒情况可能有用。
