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

Journal Article · Thu Jan 01 04:00:00 EST 1981 · Somatic Cell Genet.; (United States)

DOI:https://doi.org/10.1007/BF01544750· OSTI ID:5748831

Meuth, M

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 ovay (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 as 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 concentration of EtMes to obtain this maximum in conditions giving low dCTP/dTTP. These results are consistent with a common mechanisms: mispairing of thymine with the O2and-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.

• Research Organization: Institut de Recherches Cliniques de Montreal, Monteal, Quebec
• OSTI ID: 5748831
• Journal Information: Somatic Cell Genet.; (United States), Journal Name: Somatic Cell Genet.; (United States) Vol. 7:1; ISSN SCGTD
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550300* -- Cytology
550400 -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
AZINES
DNA
EMS
ESTERS
GENES
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDUCTION
MUTAGENS
MUTATIONS
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
PYRIMIDINES
SULFONIC ACID ESTERS
THYMINE
URACILS