TESTOSTERONE PRETREATMENT ENHANCES CADMIUM-INDUCED INCREASES IN c-myc AND c-jun TRANSCRIPT LEVELS IN L6 MYOBLASTS

• Published in: Toxic substance mechanisms Vol. 18; no. 3; pp. 129 - 137
• Main Authors: Shimada, Hideaki, Achanzar, William, Waalkes, Michael P., Hochadel, James F.
• Format: Journal Article
• Language: English
• Published: Informa UK Ltd 01.06.1999
• Subjects: Aberrant Gene Expression; Cadmium; Myoblasts; Testosterone
• ISSN: 1076-9188
• DOI: 10.1080/107691899229098

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-induced increases of proto-oncogene transcripts, an observation that may have implications in cadmium carcinogenesis.