Carcinogenicity of 2-Acetylaminofluorene and N-Hydroxy-2-acetylaminofluorene in the Rabbit¹

Rabbits fed either 70 mg of 2-acetylaminofluorene or 50 mg of N-hydroxy-2-acetylaminofluorene daily for 56 weeks gained less weight and showed a decrease in survival time as compared to controls. Only 8/19 rabbits fed 2-acetylaminofluorene and 3/6 animals fed N-hydroxy-2-acetylaminofluorene survived for 56 weeks, whereas 12/15 control rabbits lived. Hyperplasia (in 10/19 rabbits) and squamous metaplasia (in 2/19 rabbits) of the epithelium of the urinary tract were observed in rabbits fed 2-acetylaminofluorene and hyperplasia was seen in 2/6 animals fed N-hydroxy-2-acetylaminofluorene. Tumors were found only in the urinary tract of the rabbits fed 2-acetylaminofluorene (3/19 animals with tumors) or N-hydroxy-2-acetylaminofluorene (1/6 rabbits) except for 1 adenocarcinoma of the uterus in a rabbit fed 2-acetylaminofluorene. One of 7 female control rabbits had a leiomyosarcoma of the uterus. In a second group of experiments, either 2-acetylaminofluorene or N-hydroxy-2-acetylaminofluorene (30 mg/kg) was given to rabbits intraperitoneally 3 times weekly for 40 weeks. All control rabbits (12/12) and 2-acetylaminofluorene-injected rabbits (14/14) survived 40 weeks whereas only 9/17 of the rabbits receiving N-hydroxy-2-acetylaminofluorene lived 40 weeks. Average weight gains for the 40-week period were: controls, 2.06 kg; 2-acetylaminofluorene injected, 1.58 kg; and N-hydroxy-2-acetylaminofluorene injected, 0.93 kg. The only tumor in the control rabbits was 1 leiomyosarcoma of the uterus. Two of 14 rabbits injected with 2-acetylaminofluorene had undifferentiated tumors in the abdominal wall and 1 had carcinoma of the urinary bladder. The rabbits injected with N-hydroxy-2-acetylaminofluorene had a high incidence (10/17 rabbits) of peritoneal sarcomas. In addition, 1 had a sarcoma arising in the wall of the cecum and 1 had an adenocarcinoma of the fallopian tube. N-Hydroxy-2-acetylaminofluorene was also locally carcinogenic when injected subcutaneously as the cupric chelate, tumors being produced in 3/14 rabbits. The results of these studies in the rabbit showed that N-hydroxy-2-acetylaminofluorene was more toxic than 2-acetylaminofluorene and more carcinogenic at the site of injection, but it was not more active than 2-acetylaminofluorene as a systemic carcinogen in this species.