Enhanced DNA repair as a mechanism of resistance to cis-Diamminedichloroplatinum(II)

Journal Article · Tue Jun 28 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00413a022· OSTI ID:6765431

Eastman, A; Schulte, N

Murine leukemia L1210 cells, either sensitive or resistant to the toxic action of the cancer chemotherapeutic agent cis-diamminedichloroplatinum(II), have been studied for potential differences in the formation and repair of drug-induced DNA damage. The sensitivity for these experiments was obtained by using the radiolabeled analogue (/sup 3/H)-cis-dichloro(ethylenediamine)platinum(II). The resistant cells demonstrated a 40% reduction in drug accumulation but a qualitatively similar profile of DNA-bound adducts. These adducts resembled those previously characterized in pure DNA and represented intrastrand cross-links at GG, AG, and GNG (N is any nucleotide) sequences in DNA. Repair of these cross-links occurred in a biphasic manner: rapid for the first 6 h and then much slower. The resistant cells removed up to 4 times as many adducts during the rapid phase of repair. The extent of this repair did not directly correlate with the degree of resistance in that cells with 100-fold resistance were only slightly more effective at repair than cells with 20-fold resistance. Therefore, although enhanced DNA repair is thought to contribute markedly to drug resistance, other mechanisms for tolerance of DNA damage may also occur in these cells.

• Research Organization: Univ. of Nebraska Medical Center, Omaha (USA)
• OSTI ID: 6765431
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:13; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBON 14 COMPOUNDS
DISEASES
DNA
DNA REPAIR
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
LABELLED COMPOUNDS
LEUKEMIA
MAMMALS
MICE
MOLECULAR BIOLOGY
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PLATINUM COMPOUNDS
RECOVERY
REPAIR
RODENTS
SENSITIVITY
TRANSITION ELEMENT COMPOUNDS
TRITIUM COMPOUNDS
TUMOR CELLS
VERTEBRATES