Vol. 289, Issue 2, 825-830, May 1999

Differences in Cadmium Transport to the Testis, Epididymis, and Brain in Cadmium-Sensitive and -Resistant Murine Strains 129/J and A/J

Laura M. King, William A. Banks and William J. George

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana

Although most animals with scrotal testes are susceptible to cadmium-induced testicular toxicity, strain-related differences are seen in mice. Resistant murine strains demonstrate a decreased cadmium concentration in the testis and also in the epididymis and seminal vesicle. In this study we analyzed cadmium transport into tissues with a vascular barrier, the testis, epididymis, and brain, in an attempt to characterize the mechanisms of strain resistance to cadmium-induced testicular toxicity. In the resistant murine strain A/J, ¹⁰⁹Cd transport (administered as ¹⁰⁹CdCl₂) was significantly attenuated in the testis, epididymis, and brain, when compared to the sensitive murine strain 129/J. The unidirectional influx constant (K_i, in µl g¹ min¹) for ¹⁰⁹Cd was 0.01929 in the A/J testis as compared with 1.174 in the 129/J testis (P < .0001). The percentage of a ¹⁰⁹Cd dose that reached the A/J testis by 60 min was over 10 times less than that which reached the 129/J testis. The transport system used by cadmium in the 129/J testis was saturable, with 20 µM unlabeled cadmium chloride inhibiting transport by over 60%. The transporter was competitively inhibited by zinc (P = .00017), but not by calcium, indicating a specificity in ion transport. Studies with isolated tubules and analysis of testicular fluid compartments demonstrated no significant difference in cadmium uptake or efflux between the strains when corrected for the amount of ¹⁰⁹Cd entering the testis. Therefore, murine strain differences in testicular sensitivity to cadmium appear to be related to the variable presence of a transport system for cadmium in the testicular vasculature.