Gross and cellular response of intestinal crypts to single and fractionated doses of vincristine plus radiation: the influence of time between modalities.

The response of intestinal crypts to single doses and four equal, daily fractions of vincristine (VCR) plus gamma-rays, has been measured by the crypt microcolony assay. Measurements were made for VCR given either 7 hours or 1 min before radiation. For the 7-hour interval, fractionating the VCR dose markedly increased the efficacy of the combination treatment. However at 1-min interval, no injury additional to that for gamma-rays alone could be demonstrated, with either one or four fractions. Histopathological studies showed that both VCR and gamma-rays alone caused cell death, but with different distributions in the crypt. For combined treatments, both VCR-and gamma-type damage could be recognized with the 7-hour interval, but at 1 min only gamma damage. It is suggested that mitotic delay induced by radiation may permit the repair of injury caused by simultaneously-delivered VCR.