A METHOD OF ASSAY OF ANTITUMOR ACTIVITY USING A RAT MAMMARY FIBROADENOMA

Abstract
An assay method for investigation of factors which influence growth rate of a benign mammary fibroadenoma of female rats has been described. Variations in number of absolute tumor "takes, " final tumor size and variable growth rates, necessitates employment of a definitely established, growing tumor for routine assay purposes. Marked differences exist between response of mammary fibroadenomas to early treatment and treatment after tumors are growing autonomously. Since established tumors more nearly simulate the tumors dealt with in clinical medicine, studies of tumors of this may provide correlations between laboratory and clinical observations. Ovariectomy retards growth rate of established mammary fibroadenomas; adrenalectomy induces only a slight inhibitory effect; but both procedures combined result in greater inhibition of tumor growth. Estradiol cyclopentylpropionate, at dose levels which inhibit growth rate of initially transplanted tumors, stimulates growth rate of established tumors. Progesterone, which stimulates tumor growth if administered from day 1 of transplantation, has no effect on subsequent tumor growth if administration is initiated after tumors are well established. Hydrocortisone, if given in amounts adequate to prevent body growth, has no effect on growth of established tumors. However, administration of similar amounts of the same hormone for 5 days prior to tumor implantation results in greater final tumor size 65 days later. Testosterone propionate, reference standard for this assay, has been found to consistently inhibit tumor growth but never induced regression. Testosterone cyclopentylpropionate has a biphasic effect on tumor growth, stimulating growth at low doses, inhibiting at higher doses. Tumor inhibitory effects of testosterone propionate are accompanied by ovarian and adrenal involution and preputial gland and uterine stimulation. Four groups of controls are required for an assay of this type: initial tumor implant weights (1 of every 10 implants), pretreatment controls (35 days following implantation), final controls (65 days following implantation) and hormonal controls (1.0 mg of testosterone propionate each day from day 35 to day 65).