Carcinogenesis of the Uterine Cervix in Mice: Effect of Diethylstilbestrol After Limited Application of 3-Methylcholanthrene2

Abstract

Interrelationships between a chemical carcinogen and hormonal status in cervical carcinogenesis were investigated. No significant effect of castration or added estrogen stimulation was detected under conditions of prolonged exposure to methylcholanthrene by cervical painting or continuous exposure of the endocervical epithelium to a methylcholanthrene-coated thread. When the time of exposure to methylcholanthrene-coated threads was reduced to 4 weeks, a low incidence of cervical carcinoma appeared in castrates, providing a base line for determination of the effect of subsequent systemic treatment with estrogenic hormone. The incidence of cervical carcinoma was increased and the average latent period decreased in strains A/Sn, C3HeB/FeJ, and 129/J when systemic treatment with diethylstilbestrol followed a 4-week exposure of the castrate endocervical epithelium to a methylcholanthrene-coated thread. The incidence of carcinoma increased from 13.2 to 90.2 percent when 33 percent diethylstilbestrol-cholesterol pellets were administered. The average latent period was reduced from 12.3 to 6.7 months. Ten percent diethylstilbestrol-cholesterol pellets increased the incidence of carcinoma from 3.3 to 19.1 percent with lesser shortening of the average latent period. Plain-thread stimulation of the castrate endocervical epithelium for 4 weeks followed by 33 percent diethylstilbestrol pellets produced an incidence of 7.1 percent carcinoma in the three strains. Ten percent diethylstilbestrol pellets produced carcinoma in 1.5 percent of strain A castrates. Plain-thread stimulation for 4 weeks produced no carcinomas among 78 mice. The “promoting” action of estrogen in these experiments is discussed.