Testosterone pretreatment enhances cadmium-induced increases in c-myc and c-jun transcript levels in 16 myoblasts

Cadmium is a known carcinogen that often targets male reproductive tissues. In many cells cadmium induces expression of the proto-oncogenes c-myc and c-jun. Several steroid hormones can modify the effects of cadmium, including testosterone. Thus, we studied the effects of testosterone on cadmium toxicity or c-myc and c-jun expression in L6 cells. Testosterone at non-toxic doses (0-10 muM) did not modify either cadmium-induced cytotoxicity or expression of metallothionein, a protein involved in acquired cadmium tolerance. Cadmium (5 muM) increased c-myc and c-jun m RNA levels by 3.1-fold and 2.8-fold of control, respectively. Testosterone alone (10 muM) decreased basal levels of c-myc transcript but did not affect c-jun. Despite reducing transcript levels by itself, testosterone pretreatment increased cadmium-induced c-myc transcript accumulation to 5-fold over control. Testosterone pretreatment also enhanced cadmium induction of c-jun mRNA accumulation. Thus, it appears that testosterone increases cadmium...