Biomaterial Database

Clofibrate enhances the DNA damaging action and cytotoxicity of nitrosoureas. 1993

T Lawson, and P R Gwilt

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805.

The ability of N-ethyl-N-nitrosourea (ENU) to produce single strand breaks (SSB) and N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) to produce SSB and DNA-DNA interstrand cross-links was measured in L1210 cells that had been pretreated with clofibrate (CLO). When ENU was used the SSB frequency rose from 12.4 +/- 1.6/10(6) bases in control cells to 17.3 +/- 1.5/10(6) bases in CLO-treated cells and from 2.8 +/- 0.1/10(6) bases in control cells to 5.5 +/- 0.4/10(6) in CLO-treated cells when BCNU was the damaging agent. Similarly the cross-linking frequency rose from 3.5 +/- 0.1/10(6) bases in control cells to 12.1 +/- 0.5/10(6) bases in CLO-treated cells when BCNU was the cross-linking agent. CLO treatment increased the production of superoxide anion four-fold over the controls and it increased the cytotoxicity of BCNU. Forty-two percent of the control+BCNU cells survived after 24 h whereas only 24% of the CLO+BCNU cells survived. The stimulation of the diffuse condition known as oxidative stress increased the interaction of nitrosoureas with DNA and resulted in increased biological responses, e.g. cytotoxicity.

UI	MeSH Term	Description	Entries
D007939	Leukemia L1210	An experimental LYMPHOCYTIC LEUKEMIA of mice.	Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D002330	Carmustine	A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)	BCNU,1,3-Bis(2-Chloroethyl)-1-Nitrosourea,BiCNU,FIVB,N,N'-Bis(2-Chloroethyl)-N-Nitrosourea,Nitrumon
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002994	Clofibrate	A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)	Athromidin,Atromid,Atromid S,Clofibric Acid, Ethyl Ester,Ethyl Chlorophenoxyisobutyrate,Miscleron,Miskleron,Chlorophenoxyisobutyrate, Ethyl
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004273	DNA, Neoplasm	DNA present in neoplastic tissue.	Neoplasm DNA
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005038	Ethylnitrosourea	A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.	Nitrosoethylurea,N-Ethyl-N-nitrosourea,N Ethyl N nitrosourea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus