Selective protection of non-cancer cells by hypothermia.
Anticancer Res
; 22(6A): 3267-72, 2002.
Article
en En
| MEDLINE
| ID: mdl-12530074
ABSTRACT
BACKGROUND:
A serious limitation in cancer treatments is insufficient selectivity of drugs for cancer cells. We have previously demonstrated that, in contrast to p53-deficient cells, cells with wild-type p53 undergo a reversible cell cycle arrest when incubated at 28 degrees C instead of 37 degrees C. Since most of the human tumors are p53-deficient, it suggests that hypothermia may selectively protect normal cells from cytotoxic treatments that primarily target proliferating cells. MATERIALS ANDMETHODS:
We have examined the effect of hypothermia on the survival of wild-type and p53-deficient cells exposed to the anti-tumor drug 5-fluorouracil and compared BrdU incorporation at 28 degrees C and 37 degrees C of normal and tumor cells.RESULTS:
p53 wild-type fibroblasts, in contrast to p53-deficient cells, survive much higher doses of 5-fluorouracil when incubated at 28 degrees C than at 37 degrees C. Among tumor cells, the loss of the p53 function coincides with the inability to arrest cell cycle progression at low temperature and with increased sensitivity to prolonged hypothermia as a single modality.CONCLUSION:
Hypothermia protects normal cells from cytotoxic treatments and may improve the therapeutic index of chemotherapy by mechanisms based on the differences in cell cycle regulation between normal and tumor cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibroblastos
/
Fluorouracilo
/
Hipotermia Inducida
/
Antimetabolitos Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos