Hyperthermic enhancement of cis-diamminedichloroplatinum (II)-induced DNA damage in human esophageal cancer transplantable to nude mice.
The effects of a combination of cis-diamminedichloroplatinum (II) (CDDP) and hyperthermia on tumor growth were examined using nude mice bearing a transplantable human esophageal cancer (ESO-2). A combination of 4 mg/kg CDDP and 43 degrees C hyperthermia for 30 min effectively inhibited tumor growth in comparison with either treatment alone. Whereas the S-phase fraction was decreased for only 3 days with hyperthermia alone, it was decreased for at least 7 days with the combination of CDDP and hyperthermia. Though the intratumoral concentration of CDDP in the heated tumor was 1.4 times higher than that in the unheated tumor, the amount of DNA-bound CDDP in the heated tumor was 2.2 times higher. The repair efficiencies of CDDP-induced DNA damage showed no significant difference between the heated tumor and the unheated tumor. Therefore, it is suggested that the enhancement of the antitumor effects of CDDP by hyperthermia is dependent on the increase in the initial amount of CDDP-induced DNA damage.
Yano
T
T
First Department of Surgery, Nara Medical University, Kashihara, Japan.
Nakatani
K
K
Nakano
H
H
Ihara
M
M
Ohnishi
T
T
D000368:Aged; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D003131:Combined Modality Therapy; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013997:Time Factors; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm; D002945:Cisplatin