Influence of cis-diamminedichloroplatinum (II) on mouse duodenal crypt stem cell survival after multifraction X ray treatment

Abstract

The mechanism of interaction of cis-platinum and X rays was investigated in mouse duodenal crypts using the microcolony assay. Mice were exposed to 1, 2, 5, 10, or 15 fractions of X rays, either alone or preceded by a single i.p. injection of cis-platinum, 8 mg/kg, one-half hour before the first fraction. In all fractionation regimens, cisplatinum caused as shift of the X ray survival curve for crypt cells towards lower doses. The vertical distances between the survival curves after X rays and those in combination with cis-platinum were about the same, giving a mean value of 0.89 ± 0.12 log 10 cells. After cis-platinum treatment alone, a crypt cell survival curve was established in the high dose range. The estimated cell kill by 8 mg/kg of cis-platinum, obtained by extrapolation of this curve, was 1 log 10 cell number. These data imply independent cell killing mechanisms for cis-platinum and X rays. However, even after correction for cell kill by the drug, cis-platinum tended to inhibit slightly sublethal damage repair after X rays. This was supported by linear quadratic analyses, in which the α β value after combined treatment was found to be slightly higher than after X rays alone (20 ± 4 Gy versus 13.0 ± 1.7 Gy).