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The effect of estrogen on cell proliferation in the descending colon of the mouse as an example of a non-target organ was investigated. Ovariectomized mice were given single or multiple injections of 10 ng/g body weight of 17 beta-estradiol and were killed 1 h after 3H-thymidine injection. Estrogen treatments decreased incorporation of 3H-thymidine into the DNA of colonic mucosa most markedly at 4 h after the single or the last of multiple injections. The inhibitory effect of estrogen on 3H-thymidine incorporation was greater and lasted longer after a single injection than after multiple ones. A similar inhibitory effect was observed in the colonic mucosa of male mice as well as in the mucosa of mice in which colonic epithelial cell proliferation was enhanced by refeeding after 48 h of fasting. However, the colonic mucosa of mice treated with estrogen implants for up to 4 days was not affected. Estrogen treatments caused no significant change in the DNA, RNA and protein contents of the colonic mucosa. The efficacy of estrogen treatments was verified by an increase in both the wet and dry weights of the uterine horns of ovariectomized mice.

Recall bias in retrospective studies among cases reporting events which occur prior to diagnosis is difficult to measure. In this paper breast self-examination (BSE) practice as reported in a general population survey of 395 women is compared to data on BSE practice from six recent retrospective case-control studies of breast cancer. The focus is on the change in reported level of BSE practice which is associated with a change in the level of related study variables. The patterns of these differences in reported BSE practice are compared for the available categories of age, education, marital status, and menopausal status in each retrospective study to the corresponding pattern in the survey data. The patterns are similar except for the comparison by education. The other variables give no evidence of postdisease reporting bias. Factors other than postdisease reporting bias which might account for the education difference are discussed. Further development of a model for the impact of education on reporting bias is needed.

The capability of carcinogens with different modes of action to affect replicative DNA synthesis in the human colon was tested with the use of organ culture of histologically normal mucosae from patients undergoing colectomy for colon cancer or diverticulosis. 1,2-Dimethylhydrazine, an organotropic carcinogen for the colon in rodents, inhibited DNA synthesis of mucosa at a concentration of 3.0 mM but not at 1.5 mM. Methylazoxymethanol acetate, a proximate carcinogen, inhibited DNA synthesis at a concentration of 1.5 mM. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting carcinogen, inhibited DNA synthesis at a concentration of 0.5 mM. No tissue toxicity was observed at the doses of these carcinogens used. The procarcinogen benzo[a]pyrene, which is not organotropic for the colon, caused no inhibition of DNA synthesis in colon explants at concentrations of 0.01--0.05 mM. These data indicate that replicative DNA synthesis in the human colon is most sensitive to the inhibitory effect of the direct-acting carcinogen MNNG.

The regulatory role of estrogen on cell population kinetics in the descending colon was studied in intact female and ovariectomized mice. In the colonic crypts from intact mice, the crypt size (the number of epithelial cells per crypt column) and the proliferative activity of epithelial cells fluctuated slightly during the estrous cycle. Peak cellularity per crypt column was exhibted during estrus and early diestrus, whereas peaks in labeling index were seen during estrus and late metestrus. While the population size of mucous cells showed a minimal variation, the number of proliferative vacuolated cells per crypt column varied inversely with that of differentiated columnar cells during estrous cycle. The vacuolated cells were increased in number in the preovulatory phase and the columnar cells in the postovulatory phase. Three weeks after bilateral ovariectomy, the colonic crypt appeared to reach a new steady state, which was characterized by a small crypt size, a decrease in the number of differentiated cells, an increase in the relative number of proliferative cells and a relative increase in the proliferative activity of the crypt as compared to intact mice. When ovariectomized mice were treated with estrogen, the number of 3H-thymidine-labeled cells in the crypt was decreased as compared to untreated ovariectomized mice, the decrease being greater after a single injection than after multiple injections of estrogen, and the vacuolated-columnar cell line being affected more than mucous cell line. Meanwhile, the crypt size as well as the population size of differentiated cells in the crypt failed to return to normal after estrogen treatments. Thus, estrogen did not promote differentiation of epithelial cells in the crypt.