Cocarcinogenesis between cadmium and Aroclor 1254 in planarians is enhanced by inhibition of glutathione synthesis.

Asexual Dugesia dorotocephala planaria continuously exposed to 50 micrograms/beaker of Aroclor 1254 (A1254) and cadmium (Cd) developed tumors after 11 days of continuous exposure to 0.65 or 1.3 mg/liter Cd and after 23 days to 0.13 mg/liter Cd. The tumor rate at 14 days averaged 53% for the survivors in both 0.65 and 1.3 mg/liter Cd + A1254 and 40% at 0.13 mg/liter Cd + A1254. Other groups were either preexposed or coexposed to L-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione synthesis. In the presence of A1254 (50 micrograms/beaker), animals continuously exposed to BSO and 0.13 mg/liter Cd first developed tumors at 18 days, with a tumor yield equal to 41% of the survivors. Tumors developed by 6 days at 0.65 mg/liter Cd, with a yield equal to 75% of survivors. At 1.3 mg/liter Cd, BSO did not change the rate or frequency of planarian tumor production. Continuous BSO always produced high mortality over 20 days. In contrast, a 24-h preexposure to BSO caused little mortality. In these groups, tumor yields increased with cadmium concentration (0.13, 0.25, 0.65 mg/liter), and the large cocarcinogenic effect of A1254 was clearly evident. No tumors developed in animals exposed only to 50 micrograms/beaker of Aroclor 1254 or continuously only to 1 mM BSO.