Lx. Yang et al., ENHANCED RADIATION-INDUCED CELL-KILLING BY CARBOPLATIN IN CELLS OF REPAIR-PROFICIENT AND REPAIR-DEFICIENT CELL-LINES, Radiation research, 144(2), 1995, pp. 230-236
The objective of this study was to determine whether a deficiency for
either one of two repair processes influences the phenomenon of enhanc
ement of radiation-induced cell killing by carboplatin which has been
reported previously in one cell line (V79) and which is presumably a r
esult of an interaction between these two therapeutic modalities. Cell
killing was enhanced in cells of four cell lines when the cells were
exposed to carboplatin before and during irradiation in either air or
hypoxia. In cell lines proficient in both excision repair and DNA doub
le-strand break repair (K1 and AA8), and in a cell line deficient in n
ucleotide excision repair (UV41), the enhancement was characterized as
both a reduction in the shoulder region of the survival curves indica
ted by a reduced D-q and a reduction in D-O in the terminal region of
the survival curves determined for cells exposed in air and under hypo
xic conditions. Only the latter effect was observed in a cell line def
icient in DNA double-strand break repair (xrs-5). The survival curves
were fitted to the data using the repair saturation model and a comput
er program developed by N. Albright (Radiat. Res. 118, 112-130, 1989).
In hypoxia, the reductions in D-q were as great as from 7.0 Gy to 2.1
Gy, 3.3 Gy to 0 Gy and 1.7 Gy to 0 Gy for K1, AAS and UV41 cells, res
pectively. Sensitizer enhancement ratios ranged from 1.3 to 1.7 and we
re similar for irradiation in air and under hypoxic conditions. This e
nhanced cell killing by carboplatin combined with radiation required l
evels of the drug sufficient to produce cytotoxicity by the drug alone
as exemplified by the UV41 cell line, which is intrinsically sensitiv
e to carboplatin and in which (1)/30 of the drug concentration require
d for the other cell lines produced an enhanced cell killing at an equ
itoxic dose of only 5 mu M. (C) 1995 by Radiation Research Society