Hypothermic modulation of doxorubicin, cisplatin and radiation cytotoxicity in vitro.
BACKGROUND
The influence of hypothermia on doxorubicin, cisplatin and radiation cytotoxicity was investigated in vitro.


METHODS
A human glioma cell line (251MG) in early exponential growth was exposed to doxorubicin or cisplatin at various concentrations for 4 hours, or X-irradiation at 28 degrees C or 37 degrees C. The cells continued growing in multi-well plates at 37 degrees C and were counted every third day until the end of the logarithmic phase, on day 13.


RESULTS
Exposure to doxorubicin 0.05-0.5 microg/ml or cisplatin 1-10 microg/ml caused a dose-dependent inhibition of cell growth with a significantly reduced toxicity when exposed at 28 degrees C as compared to 37 degrees C. Irradiation with 4 Gy also resulted in less toxicity during hypothermia. Chlorpromazine 0.01-10 microg/ml, used to induce hypothermia in vivo (1), neither influenced, cellular growth itself nor interacted with doxorubicin, cisplatin or irradiation.


CONCLUSIONS
Moderate hypothermia (28 degrees C) appears to protect against the cellular insult of doxorubicin, cisplatin and ionising irradiation and their consequences.
Lundgren-Eriksson
L
L
Department of Radiation Sciences, Oncology, Umeå University, Sweden. lotta.lundgren.eriksson@onkologi.umu.se
Hultborn
R
R
Henriksson
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002746:Chlorpromazine / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004317:Doxorubicin; D002945:Cisplatin; D002746:Chlorpromazine