Abstract
The rapid induction of hyperplastic foci and adenomas of the Harderian gland by treatment with N-ethyl-N-nitrosourea (ENU) followed by administration of urethane (UR) was studied in male B6C3F1 mice. The mice were initiated intraperitoneally with ENU (40, 60, or 90 mg/kg body wt) once a week for 3 weeks, and given drinking water containing UR (600 ppm) from 1 week after the last exposure to ENU. Light microscopic examination of the Harderian gland was conducted 20, 25, and 30 weeks after the first treatment of ENU to examine sequential changes induced by ENU and/or UR. In mice treated with 40 mg/kg body wt of ENU alone, hyperplastic foci and adenomas were found from week 25, but there were no significant differences in the development of these lesions compared with the vehicle control group until week 30. UR significantly increased the development of ENU (40 mg/kg)-induced hyperplastic foci and adenomas at weeks 25 and 30, respectively, compared with the ENU(40 mg/kg)-alone and UR-alone groups. Magnitudes of initiation by 60 and 90 mg/kg body wt of ENU were too strong to assess the promoting effect of UR. The present results indicate the usefulness of a two-stage system comprising ENU initiation as an in vivo short-term test for carcinogenetic modulators of the mouse Harderian gland.
