Biomaterial Database

In vivo DNA damage and resistance to 1-methyl-1-nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea in L1210 leukemia cells. 1988

L B Gorbacheva, and G V Kukushkina, and A D Durdeva, and N A Ponomarenko

Institute of Chemical Physics, Academy of Sciences of the USSR.

Damages in secondary DNA structure and inactivation or activation of some repair enzymes such as DNA polymerases alpha and beta and poly(ADP-riboso)polymerase induced by 1-methyl-1-nitrosourea (MNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) after administration of the drugs at therapeutic single doses to mice bearing parent L1210 leukemia cells (L1210/0) and MNU- and BCNU-resistant L1210 leukemia cells (L1210/MNU and L1210/BCNU) were studied. Damages in DNA structure of all three leukemia strains were investigated using centrifugation on alkaline or neutral sucrose gradients. More MNU-induced single-strand breaks (SSB) and alkali-labile lesions in L1210/0 and L1210/MNU cells were revealed in newly replicated DNA as compared with those in preexisting DNA. BCNU induced fewer SSB in newly replicated DNA of L1210/0 cells than MNU. The fastest repair of the damages in newly replicated DNA was detected in L1210/BCNU and especially in L1210/MNU cells as compared with L1210/0 cells. These results suggest that there are prone errors in the repair of DNA template as many SSB were revealed in the newly replicated DNA synthesized on the repaired DNA. Repair of DNA damages in L1210/BCNU and especially in L1210/MNU cells was accompanied by activation of DNA polymerases alpha and beta and poly(ADP-riboso)polymerase. It was shown that both DNA polymerases alpha and DNA polymerase beta were involved in the repair of damages induced by MNU and only DNA polymerase beta was involved in repair of damages induced by BCNU.

UI	MeSH Term	Description	Entries
D007939	Leukemia L1210	An experimental LYMPHOCYTIC LEUKEMIA of mice.	Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D008770	Methylnitrosourea	A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.	Nitrosomethylurea,N-Methyl-N-nitrosourea,NSC-23909,N Methyl N nitrosourea,NSC 23909,NSC23909
D011065	Poly(ADP-ribose) Polymerases	Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.	ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
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
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
D004259	DNA-Directed DNA Polymerase	DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.	DNA Polymerase,DNA Polymerases,DNA-Dependent DNA Polymerases,DNA Polymerase N3,DNA Dependent DNA Polymerases,DNA Directed DNA Polymerase,DNA Polymerase, DNA-Directed,DNA Polymerases, DNA-Dependent,Polymerase N3, DNA,Polymerase, DNA,Polymerase, DNA-Directed DNA,Polymerases, DNA,Polymerases, DNA-Dependent DNA
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D004996	Ethidium	A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide.	Ethidium Bromide,Homidium Bromide,Novidium,Bromide, Ethidium,Bromide, Homidium
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