Biomaterial Database

Postreplication repair of alkylation damage to DNA of mammalian cells in culture. 1975

Y Fujiwara

Incorporation and alkaline sucrose sedimentation studies of DNA from mouse L-cells have demonstrated the following effects of N-methyl-N-nitrosourea (MNU) and methyl methanesulfonate (MMS). Increasing the concentration of both agents increases the number of single-strand breaks or alkali-labile lesions of existing DNA, which affects the incorporation of [3H]thymidine into DNA by reducing its relative rate. DNA that is newly synthesized during the 1st hr in [3H]thymidine after MNU treatment is of lower molecular weight than is existing DNA with alkali-labile lesions in treated cells and is also lower than DNA synthesized in control cells. Such small segments formed in treated cells are elongated and joined to form high-molecular-weight DNA in the subsequent 4-hr chase in thymidine or 5-bromo-2'-deoxyuridine. Near-ultraviolet photolysis selectively degrades 5-bromo-2'-deoxyuridine-elongated DNA to segments that are nearly as small as those before chase. Further, caffeine (2 mM) present during the thymidine chase prevents nascent-strand elongation, although caffeine-insensitive chain growth occurs partly in MNU-alkylated cells. The MMS lesion (single-strand breakage in alkali) in existing DNA also temporarily interrupts replicative synthesis and makes short segments, but their elongation seems insensitive to caffeine. Our results indicate that MNU may produce both caffeine-sensitive interruptions (probably gaps), as ultraviolet damage does, and apurinic site-directed, caffeine-insensitive interruptions in nascent strands, while MMS may cause exclusively the latter. Further evidence for this is the caffeine potentiation of only MNU killing, like ultraviolet killing, of L-cells. The extent of such a specific MNU lesion is estimated to be no more than 4% of the total extent of methylation, predicting that the lesion that is accessible to caffeine-sensitive repair will be a minor product(s) other than N7-methylguanine. Mutagenic and carcinogenic effects of MNU, which are higher than those of MMS, could be ascribed to such a particular MNU lesion(s) and its repair.

UI	MeSH Term	Description	Entries
D007739	L Cells	A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.	Earle's Strain L Cells,L Cell Line,L Cells (Cell Line),L-Cell Line,L-Cells,L-Cells, Cell Line,L929 Cell Line,L929 Cells,NCTC Clone 929 Cells,NCTC Clone 929 of Strain L Cells,Strain L Cells,Cell Line L-Cell,Cell Line L-Cells,Cell Line, L,Cell Line, L929,Cell Lines, L,Cell, L,Cell, L (Cell Line),Cell, L929,Cell, Strain L,Cells, L,Cells, L (Cell Line),Cells, L929,Cells, Strain L,L Cell,L Cell (Cell Line),L Cell Lines,L Cell, Strain,L Cells, Cell Line,L Cells, Strain,L-Cell,L-Cell Lines,L-Cell, Cell Line,L929 Cell,Strain L Cell
D008698	Mesylates	Organic salts or esters of methanesulfonic acid.	Mesilate,Methanesulfonates,Mesilates,Mesylate,Methylenesulfonates
D008741	Methyl Methanesulfonate	An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.	Methylmethane Sulfonate,Dimethylsulfonate,Mesilate, Methyl,Methyl Mesylate,Methyl Methylenesulfonate,Methylmesilate,Mesylate, Methyl,Methanesulfonate, Methyl,Methyl Mesilate
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
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D009607	Nitrosourea Compounds	A class of compounds in which the core molecule is R-NO, where R is UREA.	Compounds, Nitrosourea
D010782	Photolysis	Chemical bond cleavage reactions resulting from absorption of radiant energy.	Photodegradation
D001973	Bromodeoxyuridine	A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.	BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D002110	Caffeine	A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.	1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA