Cell cycle-related genotoxic effects of 4-nitroquinoline-1-oxide in C3H 10T1/2 cells

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:6956018

Bentley, K L.S.

The aim of this study was to determine the cell cycle sensitivity of cell killing, mutation, and neoplastic transformation produced by 4-nitroquinoline-1-oxide (4NQO), a potent mutagen and carcinogen. Studies were performed in populations of 10T1/3 cells synchronized by replacing them to low density after confluence-induced arrest of proliferation. Percent survival (RCFE), the mutation frequency (ouabain resistance), and the transformation frequency (types II and III foci) were independent of the phase of the cell cycle during which the cells were exposed to 4NQO. However, quantities of (/sup 3/H)4NQO bound to the DNA of treated cells were greatest during the G/sub 1/ phase and fell 50% as the cells entered the S phase. 4NQO induced unscheduled DNA synthesis in confluence-arrested cultures, and the cell removed 25% of bound (/sup 3/H)4NQO over a 12 hour post-treatment incubation period when treated either early in the G/sub 1/ phase or at the G/sub 1//S border. These date indicated that 4NQO induced DNA adducts were removed from the DNA Of 10T1/2 cells. DNA replication in 10T1/2 cells was markedly inhibited by 4NQO. Treatment during the G/sub 1/ phase produced delays in the onset of the S phase and a reduction in the rate of subsequent DNA synthesis. A similar decrease in rate was observed for cells exposed to 4NQO in the S phase. The reduced levels of DNA replication were largely due to the decreased number of cells synthesizing DNA. The cycle-independent responses of 10T1/2 cells to 4NQO-induced cytotoxicity, mutation, and neoplastic transformation resulted from the increase in 4NQO bound to DNA during the G/sub 1/ phase and its subsequent removal during the delay of the initiation of DNA replication.

• Research Organization: North Carolina Univ., Chapel Hill (USA)
• OSTI ID: 6956018
• Country of Publication: United States
• Language: English

Related Subjects

550301 -- Cytology-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CYCLE
CELL KILLING
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
DNA
DNA REPAIR
FIBROBLASTS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MUTATIONS
NITRO COMPOUNDS
NUCLEIC ACIDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIDINES
QUINOLINES
RECOVERY
REPAIR
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS