Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride.

The effect of the antioxidant vitamin E on the tumor-inducing ability of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was investigated in randomly bred Swiss mice. Three groups of mice that were 6 weeks of age at the beginning of the experiment received the following treatments: a) vitamin E acetate [DL-alpha-tocopheryl acetate (TA)] at a 4% dose level in a powdered diet for life; b) 1,2-DMH, 10 weekly sc injections at 20 micrograms/g body weight; c) combination of a and b treatments. The administration of TA enhanced the tumorigenicity of 1,2-DMH, as evidenced by statistically significant incidences of tumors in the duodenum, cecum, colon, rectum, and anus. The present finding apparently is in contrast with the reported inhibitory effect of TA on colon carcinogenesis by 1,2-DMH.

Strain differences in susceptibility of female mice to 1,2-dimethylhydrazine.

C3H, CBA, C57BL/6j, (CBA x C57BL/6j)F1, BALB/c, DBA/2, C3HA and AKR female mice were treated with 25 weekly s.c. injections of a solution of 1,2-dimethylhydrazine (DMH) in water at a dose level of 8 mg/kg body weight. BALB/c mice appeared to be most sensitive to the induction of epithelial colorectal (93.3%) and anal tumours by DMH. There was, however, a dissociation between the severity of the macroscopical tumour lesions in the colon of BALB/c mice and their relatively weak tendency to infiltrative growth. C3HA mice were more resistant to the induction of intestinal tumours (30.9%) but the tumours showed a deep invasion into the intestinal wall. There was no correlation between the strains and within a given strain between the development of colorectal and anal neoplasms. C3H and CBA mice strains developed a high incidence of uterine sarcomas (37.5 and 40.7%, respectively) which were not found at all in BALB/c, DBA/2 and C3HA mice and which appeared in C57BL/6j and AKR mice at low frequency (2.7 and 7.7%, respectively). C57BL/6j, BALB/c, DBA/2 and C3HA mice developed haemorrhagic lesions of the ovaries (35.1, 46.7, 62.9 and 85.7%, respectively). These lesions, which led to peritoneal haemorrhage, were one of the main causes of death in C3HA and DBA/2 strains. It seems that, with the exception of AKR mice, an inverse relationship exists between the occurrence of haemorrhagic ovarian lesions and development of uterine sarcomas in female mice treated with DMH.

Tumors of the anal region induced in mice painted with methylazoxymethanol acetate.

The carcinogenicity of methylazoxymethanol acetate (MAM acetate) was examined in 91 BALB/c mice by painting it on the anal region. Carcinomas and adenomas of the perianal sebaceous gland were induced in 23 of 24 male (96%) and 16 of 30 female (53%) mice and keratoacanthoma developed in one of 24 male mice within 30 weeks after treatment with MAM acetate. Vascular tumors of the liver and fat issue of the abdominal cavity also developed in 16 of 24 male (67%) and 3 of 30 female (10%) mice treated with this drug. Microscopic adenocarcinomas were found in the rectal mucosa of 3 of 24 male mice adjacent to the anorectal junction. The sex difference in the incidence of tumors is briefly discussed.

Carcinoma of the perianal gland and associated structures in 1,2-dimethylhydrazine treated mice.

Male C57BL/Icrf alpha t mice receiving long courses of weekly subcutaneous injections of 8.25 or 12.5 mg/kg, 1,2-dimethylhydrazine (DMH) developed perianal carcinomas as well as tumours at other sites. Tumours of the perianal gland or its associated hair root sheath and overlying skin included sebaceous gland adenocarcinomas, often with squamous metaplasia, analogous to those in the rat ear, and dysplasia, polyp formation and squamous cell carcinomas (SCC). Of 152 mice treated, 88 remained after 30 injections, and 10 out of a total of 14 tumours developed after 30 treatments. Perianal SCC without definite perianal gland association developed in 2 other animals.

Morphology and histogenesis of anal region and clitoral gland tumors induced in mice by 1,2-dimethylhydrazine.

Ninety-seven tumors induced in the anal region in female CBA and BALB/c mice by 1,2-dimethylhydrazine were examined histologically. Tumors originated mainly from the following sources: epidermis (papillomas and basal cell neoplasms), pilosebaceous complexes of the anal region (keratoacanthomas, cystic squamous cell tumors, and adenomas of the perianal sebaceous glands), and clitoral (preputial) glands (adenomas and adenoacanthomas). A subcutaneous location and late ulceration were characteristics of many tumors originating from the pilosebaceous complexes and clitoral glads. From 31 to 43% of all anal tumors were of sebaceous gland (perianal or clitoral) origin. Cystic squamous cell tumors were morphologically similar to type II keratoacanthomas of rodents. Squamous cell tumors of any origin finally became squamous carcinomas.

Tumours of the anal region induced in mice by 1,2-dimethylhydrazine.

CBA female mice treated with 1,2-dimethylhydrazine developed a high incidence of benign and malignant tumours in the anal region. Many of these tumours originated from the perianal glands rather than the epidermis.