SEQUENCE OF EXPOSURE TO CADMIUM AND ARSENIC DETERMINES THE EXTENT OF TOXIC EFFECTS IN MALE FISCHER RATS

Arsenic and cadmium are both priority hazardous substances and human c arcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well d efined. We examined the toxicity of these metals when given alone or i n alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 mu mol NaAsO2/kg, s.c.) was given 2 4 h before cadmium (10, 20, or 30 mu mol CdCl2/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortali ty in rats given the high dose of cadmium (9 survivors/10 treated) com pared to rats given cadmium alone (2/10). Arsenic pretreatment also re duced cadmium-induced hepatotoxicity: as indicated by serum glutamic o xalacetic transaminase (SGOT) activity, and markedly reduced cadmium-i nduced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal- binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 mu mol CdCl2/kg, s.c.) was give n 24 h before alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreat ment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhance d MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects again st cadmium intoxication, and cadmium pretreatment does not effect arse nic toxicity. Thus, toxic interactions of arsenic and cadmium appear t o depend on the sequence of exposure. Copyright (C) 1997 Elsevier Scie nce Ireland Ltd.