© 1987 Oxford University Press
research-article |
Investigations of the Carcinogenicity of the LH-RH Analog Buserelin (HOE 766) in Rats Using the Subcutaneous Route of Administration
Hoechst Aktiengesellschaft, P.O Box 80 03 20, 6230 Frankfurt (Main) 80, Federal Republic of Germany
A carcinogenicity study with the LH-RH analog buserelin (HOE 766) was conducted in male and female Wistar rats. The compound was administered subcutaneously daily for a period of 24 months to groups of 50 male and 50 female animals in doses of 0.0002, 0.0006, or 0.0018 mg/kg body wt, followed by a 6-month recovery period without any treatment. Male and female rats (100 each) received physiological saline and served as controls. The body weight development of all male rats was regular, but in females at all three dose levels significantly increased body weight gain in comparison to the control animals occurred. Food consumption was not affected in any group. No treatment-related changes in clinical signs and hematological parameters were noted. The chronic administration of HOE 766 did not influence the survival of the male rats while in females it was dose-dependently increased. Endocrinological examinations revealed decreased serum testosterone levels in males and reduced serum progesterone levels in females during the treatment period; the changes reverted to normal during the recovery period. Reduced weights of the testes and uteri as well as increased weights of the pituitaries and ovaries in females are compound-related. Histological examination of the ani mals which died intercurrently or were killed in extremis or at the end of the recovery period revealed irreversible and partly dose-dependent changes in testes and uterus, due to the pharmacodynamic properties of HOE 766, but gave no indication of any carcinogenic effect of the compound.