Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea resistance by gamma-irradiation or drug pretreatment in rat hepatoma cells

Journal Article · Fri Feb 15 04:00:00 EST 1991 · Cancer Research; (USA)

OSTI ID:5836715

Habraken, Y; Laval, F ^[1]

---

1. Institut Gustave Roussy, Villejuif (France)

Treatment of rat hepatoma cells (H4 cells) with various DNA-damaging agents increases the number of O6-methylguanine-DNA-methyltransferase (transferase) molecules per cell. Because the cellular resistance to chloroethylnitrosoureas depends on the number of transferase molecules, we studied the influence of pretreatment with gamma-irradiation, cis-dichlorodiammineplatinum(II), or 2-methyl-9-hydroxyellipticinium on the sensitivity of H4 cells to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The BCNU resistance depends on the gamma-ray dose and increases with time after irradiation: it is maximum when the drug is added 48 h after irradiation, which corresponds to the maximum enhancement of the transferase activity in the cells. Pretreatment with a single dose of cis-dichlorodiammineplatinum(II) or 2-methyl-9-hydroxyellipticinium also increases the cellular resistance to BCNU. This resistance is not due to a modification of the alkylation of the cellular DNA in the pretreated cells but is related to the increased transferase activity, as it is no longer observed when this activity is depleted by incubating the pretreated cells with the free base O6-methylguanine before BCNU treatment. These results suggest that tumor cells surviving after gamma-irradiation or drug treatment may become resistant to chemotherapy with chloroethylnitrosoureas.

• OSTI ID: 5836715
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 51:4; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560120 -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
DNA
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
GAMMA RADIATION
IONIZING RADIATIONS
MAMMALS
METHYL TRANSFERASES
NITROSO COMPOUNDS
NITROSOUREAS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIATION EFFECTS
RADIATIONS
RATS
RODENTS
SENSITIVITY
TIME DEPENDENCE
TOXICITY
TRANSFERASES
TUMOR CELLS
VERTEBRATES