An explanation for the ability of cytotoxic drug pretreatment to reduce bone marrow related lethality of total body irradiation (TBI). [Mice]

Journal Article · Mon Mar 01 00:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90688-5· OSTI ID:6704053

Millar, J L ^[1]; Stephens, T C; Wist, E A

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1. Inst. of Cancer Research, Sutton, England

Mice given 9 to 10 Gy total body irradiation (TBI) die a hematological death 10 to 14 days after exposure. This lethality can be avoided by pretreatment with a cytotoxic drug two days before irradiation. The best example of this is seen when 200 mg/Kg cytosine arabinoside (ara-C) is given two days before TIB. Improved survival results from an earlier onset in the recovery of marrow stem cells (CFU-s) in animals given ara-C before irradiation as compared to controls. In animals given radiation alone there is a lag phase in the recovery of CFU-s; drug pretreatment before irradiation abolishes this delay. We postulate that the cells that repopulate the CFU-s compartment after irradiation are a sub-population of the DFU-s with higher self-renewal capability, lower proliferative activity and higher radiosensitivity (D/sub 0/ = .8 Gy) than the overall population D/sub 0/ = 1.1 Gy). Further, we suggest that drug pretreatment alters the radiosensitivity of the first population, increasing it temporarily to that of the overall population. This may come about by ara-C triggering these CFU-s into a relatively radioresistant phase of the cell cycle. In the Lewis lung tumor ara-C pretreatment does not affect the response to radiation, even at times when the drug promotes the early recovery of the CFU-s. It would therefore seem that a potentially useful gain in the therapeutic index may result from these findings.

• OSTI ID: 6704053
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 8:3/4
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CYTOSINE
RADIOSENSITIVITY EFFECTS
RADIATION SYNDROME
RADIOINDUCTION
RADIOPROTECTIVE SUBSTANCES
BONE MARROW
EXPERIMENTAL NEOPLASMS
IONIZING RADIATIONS
LUNGS
MICE
STEM CELLS
SURVIVAL TIME
WHOLE-BODY IRRADIATION
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AZINES
BODY
DRUGS
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
IRRADIATION
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PYRIMIDINES
RADIATIONS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals