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.
Heldestad
A
A
Department of Clinical Chemistry, Umeå University, Sweden.
Jonsborg
S
S
Henriksson
R
R
Grankvist
K
K
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000037:antagonists & inhibitors*; D016923:Cell Death; D002460:Cell Line; D006224:Cricetinae; D004961:Estramustine / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D007052:Ibuprofen / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D018906:Antineoplastic Agents, Alkylating; D004961:Estramustine; D000082:Acetaminophen; D007052:Ibuprofen