Circadian rhythm in mitotic index of corneal epithelium: presence of Ehrlich ascites carcinoma and treatment with saline or hydroxyurea.

A study of the circadian rhythm in the mitotic index (MI) of the corneal epithelium was completed in non-tumor-bearing mice and in mice bearing the Ehrlich ascites carcinoma (EAC). All mice were standardized to a light-dark cycle with 12 hours of light from 0600 to 1800 CST alternating with 12 hours of darkness from 1800 to 0600 CST. Treatments included injection with saline (SAL) or hydroxyurea (HU) at different circadian times. This investigation demonstrated that: (1) Data from untouched animals cannot serve as proper controls because treatment with SAL altered the level of the MI, but only during the diurnal, not the nocturnal, phase of the circadian cycle; (2) the presence of the EAC depressed the level of the MI, but this inhibition was only detected during the diurnal period; (3) treatment with 500 mg/kg HU injected at 0500 caused more perturbation in this rhythm than did treatment with 500 mg/kg HU at 1700; (4) when 500 mg/kg HU was given at 2000 and 0100 and 0500, the perturbation of the rhythm was greater than when 500 mg/kg HU was given at 0900 and 1400 and 1700; (5) when 3000 mg/kg HU was given at 1700 and compared to 500 mg/kg HU at 1700, little difference in the overall circadian profiles of these rhythms was observed, indicating that the circadian control mechanisms operating on the MI exerted a greater influence than did a dosage change from 500 to 3000 mg/kg HU; and (6) a comparison of the practice of plotting experimental and control data as "hours after treatment" versus using a "time of day" plot for the same data demonstrated that the "hours after treatment" plot is very misleading because it fails to account for the significant circadian oscillation in this in vivo system.