铅的细胞与分子毒理学。III. 铅对血红素合成的影响。

Cellular and molecular toxicology of lead. III Effect of lead on heme synthesis.

作者信息

Lake L, Gerschenson L E

出版信息

J Toxicol Environ Health. 1978 Jul;4(4):527-40. doi: 10.1080/15287397809529676.

Abstract

The effect of lead nitrate on the biosynthesis of heme and the cellular uptake of (59)Fe was studied in an established rat liver cell line (RLC-GAI) grown in serum-free medium. Heme synthesis was shown to be increased in lead-treated cells when determined by measuring the amount of (59)Fe incorporated into the heme fraction of cell homogenates; concomitant with increased (59)Fe incorporation into heme, cellular uptake of (59)Fe was also increased. By contrast, heme synthesis was inhibited by lead in a dose-dependent manner when determined by measuring the conversion of ((14)C) aminolevulinic acid into heme under identical experimental conditions. Cellular degradation of heme was not found to be significantly affected by lead. It is proposed that lead inhibited the biosynthesis of heme and that the increased incorporation of (59)Fe into the heme fraction of the lead-treated cells was the result of the increased uptake of (59)Fe and hence labeling of the heme molecules. Evidence is presented that suggests that only (59)Fe present in solution as a low-molecular-weight complex was accumulated in increased amounts by lead-treated cells.

摘要

在无血清培养基中培养的既定大鼠肝细胞系（RLC-GAI）中，研究了硝酸铅对血红素生物合成及（59）铁细胞摄取的影响。通过测量掺入细胞匀浆血红素部分的（59）铁量来确定，结果显示铅处理细胞中的血红素合成增加；随着（59）铁掺入血红素增加，（59）铁的细胞摄取也增加。相比之下，在相同实验条件下，通过测量（（14）C）氨基乙酰丙酸转化为血红素的量来确定，铅以剂量依赖方式抑制血红素合成。未发现铅对血红素的细胞降解有显著影响。有人提出，铅抑制血红素的生物合成，铅处理细胞的血红素部分中（59）铁掺入增加是（59）铁摄取增加的结果，因此血红素分子被标记。有证据表明，只有以低分子量复合物形式存在于溶液中的（59）铁被铅处理细胞大量积累。