Biomaterial Database

Role of deoxynucleoside triphosphate pools in the cytotoxic and mutagenic effects of DNA alkylating agents. 1981

M Meuth

The objective of these studies was to define the role of deoxynucleoside triphosphate pools in the cytotoxic and mutagenic effects of DNA alkylating agents. Survival of Chinese hamster ovary (CHO) cells after treatment with DNA alkylating agents was clearly related to the balance of the dCTP and dTTP pools--high dCTP/dTTP ratios increased the survival of CHO cells 2- to 10-fold compared to treatment in low dCTP/dTTP. Induction of mutations at three genetic loci by one agent, ethyl methane sulfonate (EtMes) was also affected by pool alterations. Although the maximum mutagenesis obtained in high or low dCTP/dTTP was not significantly different, it took considerably lower concentrations of EtMes to obtain this maximum in conditions giving low dCTP/dTTP. These results are consistent with a common mechanism: mispairing of thymine with the O6-alkylated guanine--causing both the cytotoxic and mutagenic effects of EtMes. They also suggest that alterations of dCTP/dTTP ratio may be involved in certain human genetic diseases characterized by increased sensitivity to DNA alkylating agents.

UI	MeSH Term	Description	Entries
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
D009153	Mutagens	Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.	Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D010053	Ovary	The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.	Ovaries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
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
D003412	Cricetulus	A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.	Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D003570	Cytidine Triphosphate	Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety.	CTP,CRPPP,Magnesium CTP,Mg CTP,Triphosphate, Cytidine
D003597	Cytosine Nucleotides	A group of pyrimidine NUCLEOTIDES which contain CYTOSINE.	Cytidine Phosphates,Nucleotides, Cytosine,Phosphates, Cytidine
D005020	Ethyl Methanesulfonate	An antineoplastic agent with alkylating properties. It also acts as a mutagen by damaging DNA and is used experimentally for that effect.	Ethylmethane Sulfonate,Ethyl Mesilate,Ethyl Mesylate,Ethylmesilate,Ethylmesylate,Mesilate, Ethyl,Mesylate, Ethyl,Methanesulfonate, Ethyl,Sulfonate, Ethylmethane
D005260	Female		Females