Effect of pH and moderate hyperthermia on doxorubicin, epirubicin and aclacinomycin A cytotoxicity for Chinese hamster ovary cells

Abstract

The influence of extracellular pH on the cytotoxicity of the anthracyclines doxorubicin, epirubicin, and aclacinomycin A was examined at 37° C and 41° C in tissue culture. Chinese hamster ovary (CHO) cells were exposed for a total of 24 h to anthracyclines at doses ranging between 0.12 and 0.69 nmol/ml at pH 7.4,6.7, and 6.4 and at 37° C. Temperature elevation to 41° C was carried out for 3 h after the initiation of the drug treatment. Doxorubicin and epirubicin were about equally cytotoxic in the pH range examined at both temperatures. Aclacinomycin A demonstrated a higher cytotoxicity at pH 7.4 and 37° C only at low doses. At low pH, however, aclacinomycin A was increasingly more effective with increasing dose as compared with doxorubicin and epirubicin. At 41° C and at higher doses aclacinomycin A was even less cytotoxic than doxorubicin or epirubicin. Doxorubicin and epirubicin were less effective at lower pH. However, aclacinomycin A at doses of greater than 0.25 nmol/ml was more cytotoxic at low pH. Moderate hyperthermia did not increase the cytotoxicity of the three drugs at low pH, except for aclacinomycin A at doses of less than 0.25 nmol/ml. At pH 7.4, aclacinomycin A was even less effective at the elevated temperature. At doses of greater than 0.25 nmol/ml, moderate hyperthermia decreased the cytotoxicity of aclacinomycin A at low pH.