A carcinogenicity study in mice of a beta-adrenergic antagonist, primidolol; increased total tumour incidence without tissue specificity.
The beta-adrenergic blocking agent, primidolol hydrochloride, was administered, mixed in the diet, to mice (CD-1, Charles River, France) for 18 months. Experimental groups comprised untreated controls (100/sex) and those receiving 12.5, 25 and 50 mg drug/kg body weight (50/sex). There were no non-neoplastic lesions which could be attributed to the treatment. The pattern of tumour incidence was sex-related; in females the proportion of tumour-carrying animals was significantly higher in the top dose group (48%) than in the controls (24%), whereas in males the converse was found (30% in the top dose group vs. 48% in the controls). In the top dose female group there was no one tissue in which the tumour incidence was significantly higher than in the controls. We debate whether the analysis of total tumours in the absence of a target organ is an appropriate assay for carcinogenicity. Against a background of regulatory action towards beta-blocking agents, we discuss the possibility that the results of the present study could represent either a co-carcinogenic effect of beta-blocking agents or, alternatively, a statistical contingency.
D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009928:Organ Specificity; D011412:Propanolamines / Q000633:toxicity*; D012107:Research Design; D012737:Sex Factors; D013223:Statistics as Topic
D000319:Adrenergic beta-Antagonists; D002273:Carcinogens; D011412:Propanolamines; C025720:primidolol