Waalkes M P, Perantoni A
Laboratory of Comparative Carcinogenesis, Frederick Cancer Research Facility, Maryland 21701.
In Vitro Cell Dev Biol. 1988 Jun;24(6):558-65. doi: 10.1007/BF02629091.
Cadmium (Cd) induces testicular tumors of interstitial cell (IC) origin in rats which can be prevented by zinc (Zn). Zn-induced synthesis of metallothionein (MT), a metal-binding protein with a high affinity for Cd, is thought to account for tolerance to Cd in most tissues by sequestration of Cd. However, the mechanism of Zn inhibition of Cd-induced carcinogenesis in the testes is unknown. Our studies with ICs obtained by collagenase dispersion of rat testes, indicate the levels of the Cd-binding protein in ICs are unaltered by Zn. This testicular protein also was found to differ from MT in amino acid content and to have a lower affinity for Cd. Thus, MT does not seem to be involved in protection of ICs against Cd carcinogenesis. Altered Cd toxicokinetics as a possible explanation for Zn-induced tolerance was therefore explored. Cd uptake into isolated ICs had passive diffusion and nonpassive (carrier mediated or active transport or both) components. The nonpassive component of Cd accumulation was markedly reduced by addition of Zn in vitro, indicative of competition for uptake at the cellular level. These results indicate that toxicokinetic alterations leading to reduced Cd accumulation may play an important role in Zn induction of tolerance to Cd carcinogenesis in the testes.
镉（Cd）可诱发大鼠间质细胞（IC）来源的睾丸肿瘤，而锌（Zn）能够预防这种情况。锌诱导金属硫蛋白（MT）的合成，MT是一种对镉具有高亲和力的金属结合蛋白，被认为通过螯合镉使得大多数组织对镉产生耐受性。然而，锌抑制睾丸中镉诱导的致癌作用的机制尚不清楚。我们通过胶原酶分散大鼠睾丸获得间质细胞进行研究，结果表明锌不会改变间质细胞中镉结合蛋白的水平。还发现这种睾丸蛋白在氨基酸含量上与金属硫蛋白不同，并且对镉的亲和力较低。因此，金属硫蛋白似乎不参与保护间质细胞免受镉致癌作用。因此，我们探讨了镉毒代动力学的改变作为锌诱导耐受性的一种可能解释。镉进入分离的间质细胞有被动扩散和非被动（载体介导或主动转运或两者兼有）成分。在体外添加锌可显著降低镉积累的非被动成分，这表明在细胞水平上存在对摄取的竞争。这些结果表明，导致镉积累减少的毒代动力学改变可能在锌诱导对睾丸中镉致癌作用的耐受性中起重要作用。
