EFFECTS OF AGE ON ENDOMETRIAL CARCINOGENESIS INDUCED BY CONCURRENT ORAL-ADMINISTRATION OF ETHYLENETHIOUREA AND SODIUM-NITRITE IN MICE

Aging effects on the susceptibility to chemical endometrial carcinogen esis were investigated in ICR female mice. The animals were divided in to 3 groups of different ages: 1 month (young), 6 months (middle), and 12 months (old) at initiation of treatment. They received weekly oral administration of mixture of ETU (100 mg/kg body weight) and sodium n itrite (70 mg/kg body weight) for 6 months followed by a withdrawal pe riod of 3 months. Al animals were subjected to histopathology. The inc idence of endometrial adenocarcinomas was highest in the middle age gr oup (8/20), secondary in the old age group (4/20), and lowest in the y oung group (1/20). The incidence of atypical glandular hyperplasia, a precursor lesion of the tumor, was also higher in the middle age group . The endometrial adenocarcinomas showed morphological similarities am ong all age groups and the nuclei of tumor cells lost almost ail stain ing reactivity to estrogen receptors. The labeling indices with bromod eoxyuridine (BrdU) were notably higher in the old age group than in th e young and middle age groups. A further investigation on the aging pr ocess of female genital organs in control mice revealed that their sen ility seemed to be preceded by the formation of ovarian cysts which fi rst appeared at 6 months of age with a concomitant elevation of plasma 17 beta-estradiol level. These results indicate that the susceptibili ty of the mouse endometrium to the carcinogenic effects of N-nitroso E TU could be closely linked with the stage of aging process of the geni tal organs and it appears to be most susceptible when initiated at aro und 6 months of age. However, the mitotic activity of neoplastic endom etrial glandular cells seems to be higher in older mice than younger o nes.