Influence of cis-diamminedichloroplatinum (II) on mouse duodenal crypt stem cell survival after multifraction X ray treatment.
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 a 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 log10 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 log10 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 alpha/beta value after combined treatment was found to be slightly higher than after X rays alone (20 +/- 4 Gy versus 13.0 +/- 1.7 Gy).
Dewit
L
L
Begg
A C
AC
Köhler
Y
Y
Stewart
F A
FA
Bartelink
H
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004386:Duodenum / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D051379:Mice; D011838:Radiation-Sensitizing Agents; D013047:Specific Pathogen-Free Organisms; D013234:Stem Cells / Q000187:drug effects* / Q000528:radiation effects
D011838:Radiation-Sensitizing Agents; D002945:Cisplatin