Interactions between antitumor drugs and radiation in mammalian tumor cell lines: differential drug responses and mechanisms of resistance following fractionated X-irradiation or continuous drug exposure in vitro.
Drug-resistant mammalian tumor cell lines have been derived by either fractionated x-irradiation treatment or exposure to vincristine or etoposide (VP-16-213) in vitro. Analyses of the patterns of responses expressed by these differently derived, resistant cell lines have shown variations in responses to a range of antitumor drugs depending upon the agent used to induce resistance. However, all treated cell lines express resistance to vincristine and, with one exception, to VP-16-213. Preliminary evidence has indicated that resistance to vincristine in drug-treated cells, but not x-irradiation-treated cells, is associated with impaired vincristine uptake; resistance to VP-16-213 in both differently derived, resistant sublines is associated with a reduction of VP-16-213-induced DNA single-strand breakage; and collateral sensitivity to cisplatin in x-irradiation-treated cells is associated with enhanced drug-induced DNA cross-linking. These data indicate that patterns of responses to antitumor drugs and the mechanisms associated with these altered responses differ depending upon the agent used to induce resistance.
Hill
B T
BT
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, London, England.
Whelan
R D
RD
Hosking
L K
LK
Shellard
S A
SA
Bedford
P
P
Lock
R B
RB
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects*; D014750:Vincristine / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D014750:Vincristine; D005047:Etoposide; D002945:Cisplatin