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GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE
Liu, J., C. Corton, D J. Dix, A P. Altshuller, Y. Liu, M. Waalkes, AND C. D. Klaassen. GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE. TOXICOLOGY AND APPLIED PHARMACOLOGY 176(1):1-9, (2001).
Genetic Background but not Metallothionein Phenotype Dictates Sensitivity to
Cadmium-Induced Testicular Injury in Mice
Jie Liu1,2, Chris Corton3, David J. Dix4, Yaping Liu1, Michael P. Waalkes2
and Curtis D. Klaassen1
Parenteral administration of cadmium (Cd) at sufficient doses to mammals causes testicular damage. Sensitivity to Cd-induced testicular injury varies greatly among mouse strains. For instance 129/SvJ (129) mice are highly sensitive while C57BL/6J (C57) mice are refractory to Cd-induced testicular injury. Metallothionein (MT), a Cd-binding protein, is thought to be responsible for the strain-susceptibility to Cd toxicity. In this study, MT-I/II knockout (MT-null) and wild-type 129 mice were used to determine the role of MT in Cd-induced testicular injury. Two additional strains of mice (C57 and C57x129 F1cross) were also used to help define the genetic background in Cd toxicity. Mice were given CdCl2 (5-20 mol/kg, ip) and testicular injury was examined 24 hrs later by histopathology and testicular hemoglobin concentration. Cd produced dose-dependent testicular injury in all strains of mice, except for C57 mice in which testicular injury could not be produced. MT-null mice were more sensitive than C57x129 mice, but were equally sensitive as 129 mice to Cd-induced testicular injury. Fourteen days after Cd administration (15 mol/kg, ip), testicular atrophy was evident in MT-null, 129, and C57x129 mice, but was absent in C57 mice. Additional study showed the resistance of C57 mice to Cd-induced testicular injury could not be attributed solely to a decreased uptake of 109Cd, nor to a greater amount of testicular MT. Microarray revealed a number of differentially expressed genes between C57 and 129 mice, but significance to Cd-induced injury is not immediately clear. Thus, this study demonstrates that it is genetic make-up, but not MT, that is important in determining strain-susceptibility to Cd-induced testicular injury.
The information in this document has also been funded in part by the U.S. Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.