Cisplatin sensitization by concurrent mild hyperthermia in parental and mutant cell lines deficient in homologous recombination and non-homologous endjoining repair.
The effect of mild hyperthermia on cisplatin sensitization was examined in two cell line pairs, CHO parental AA8 and irsISF, an XRCC3 mutant (deficient in homologous recombination repair), and mouse parental MEF and knockout Ku80 mutants (deficient in non-homologous endjoining repair). The results showed that mild hyperthermia 40, 41 and 42 degrees C given concurrently with cisplatin treatment caused significant sensitization. The degree of sensitization was comparable for the parental and mutant lines, indicating that these repair pathways were likely not involved in cisplatin thermal sensitization. The shorter concurrent treatments cause a larger sensitization than the longer treatments. The reasons for this are not clear, but thermotolerance may be a factor.
Raaphorst
G P
GP
Medical Physics Department, The Ottawa Hospital Regional Cancer Centre, 503 Smyth Road, Ottawa, Ontario K1H 1C7, Canada. graaphorst@ottawahospital.on.ca
Li
L F
LF
Yang
D P
DP
LeBlanc
J-M
JM
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011995:Recombination, Genetic / Q000235:genetics*; D013997:Time Factors
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; D002945:Cisplatin