Document Detail

Enhancement of 1,3-bis(2-chloroethyl)-1-nitrosourea resistance by gamma-irradiation or drug pretreatment in rat hepatoma cells.
MedLine Citation:
PMID:  1847658     Owner:  NLM     Status:  MEDLINE    
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.
Y Habraken; F Laval
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  51     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1991 Feb 
Date Detail:
Created Date:  1991-04-02     Completed Date:  1991-04-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1217-20     Citation Subset:  IM    
Groupe Radiochimie de l'ADN, Unité 247 INSERM, Institut Gustave Roussy, Villejuif, France.
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MeSH Terms
Antineoplastic Agents / pharmacology
Carcinoma, Hepatocellular / therapy*
Carmustine / pharmacology*
Cisplatin / pharmacology
Combined Modality Therapy
Dose-Response Relationship, Radiation
Drug Resistance / radiation effects*
Drug Synergism
Ellipticines / pharmacology
Gamma Rays*
Liver Neoplasms / therapy*
Methyltransferases / biosynthesis
O(6)-Methylguanine-DNA Methyltransferase
Time Factors
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Ellipticines; 154-93-8/Carmustine; 15663-27-1/Cisplatin; 58337-34-1/elliptinium; EC 2.1.1.-/Methyltransferases; EC Methyltransferase

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