The development of induced cervicovaginal carcinoma in intact and estrogen-treated, castrated mice studied by histochemical and enzyme histochemical methods.

To investigate the development of induced cervicovaginal carcinoma in mice several experiments were carried out. In 1 ex periment 3 groups of 10 C3H mice received 0.5 /zg of estradiol17/8-monobenzoate s.c. twice weekly. Two groups of mice had been ovariectomized. One of these groups had been painted on the eetocervix with chloroform. Mice of the other group received on the eetocervix 20-methylcholanthrene (20-MC) dissolved in chloroform. In the mice painted with chloroform alone 4 microcarcinomas developed. Although the intact mice produced 2 microcarcinomas, the ovariectomized mice treated with 20-MC and chloroform developed 2 microcarcinomas and 6 maerocarcinomas. Ovariectomy appeared to be a tumor-promoting factor. In another experiment it was shown that painting of the cervix with 20-MC dissolved in chloroform produced a higher incidence of epidermoid carcinoma in ovariectomized, estrogen-treated mice than in intact mice. No cervical tumors were observed in ovariectomized, estrogen-treated mice not treated with the car cinogen. By histochemical methods it was shown that preneoplastic lesions had the same enzyme pattern as the normal epi thelium, although a slight decrease of activity of some enzymes had been recorded. Carcinomas, developed in a different way, showed a characteristic enzyme pattern. Generally the activity of 5-nucleotidase, aminopeptidase, reduced nicotinamide adenine dinucleotide (NADH)and NADPH-tetrazolium reducÃ-ase, lactic acid dehydrogenase, and glucose-6-phosphate dehydrogenase increased, while the activity of alkaline phosphatase, 0-hydroxvbutyric acid dehydrogenase, and the nonspecific esterases decreased. In a 3rd experiment it was demonstrated that in ovariectomized mice estrogens alone can act as tumor-promot ing agents. The role of estrogens in the development of chemi cally induced cervicovaginal carcinomas is discussed.