In vitro assessment of target cell specificity in cadmium carcinogenesis: interactions of cadmium and zinc with isolated interstitial cells of the rat testes.
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.
Waalkes
M P
MP
Laboratory of Comparative Carcinogenesis, Frederick Cancer Research Facility, Maryland 21701.
Perantoni
A
A
D000818:Animals; D002104:Cadmium / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005033:Ethylmaleimide / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000139:chemically induced*; D007985:Leydig Cells / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000302:isolation & purification / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013736:Testicular Neoplasms / Q000139:chemically induced*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc; D011190:Potassium Cyanide; D005033:Ethylmaleimide