Acetaminophen protection against estramustine-induced cytotoxicity on cultured fibroblasts

Two commonly used analgesics, ibuprofen and acetaminophen (paracetamol) were investigated for possible influence on Chinese hamster fibroblast (V-79) cytotoxicity (measured by cells cloning ability and 86Rb accumulation) of the anti-neoplastic drugs estramustine and bleomycin in vitro. Fibroblast exposure to estramustine (80 mg/l) or bleomycin (50 mg/l), for 1 or 24 hr, reduced the number of surviving clones to approximately 35% and 50% respectively. Acetaminophen (10 or 100 mg/l), but not ibuprofen, significantly increased the number of surviving clones with estramustine. The analgesics had no effect on bleomycin cytotoxicity. The uptake of 86Rb+ (K+ analogue) by V-79 cells was reduced after incubation with 80 mg/l estramustine phosphate. Acetaminophen (30 mg/l) but not 10 mg/l acetaminophen or ibuprofen (30 or 100 mg/l), significantly protected against estramustine reduction of 86Rb accumulation. Acetaminophen inhibition of estramustine cytotoxicity is suggested to be due to reversal of estramustine-induced inhibition of cellular potassium channel ion transport.