Nicotinamide deficiency in human lymphocytes prevents the (3H)thymidine-induced adaptive response for the repair of X-ray-induced chromosomal damage

Journal Article · Sat Aug 01 00:00:00 EDT 1987 · Exp. Cell Res.; (United States)

DOI:https://doi.org/10.1016/0014-4827(87)90185-6· OSTI ID:6064892

Wiencke, J K

Human lymphocytes treated with (/sup 3/H)thymidine ((/sup 3/H)dThd) become refractory to the induction of chromosomal aberrations by subsequent doses of X rays. This adaptive response to (/sup 3/H)dThd does not occur in the presence of 3-aminobenzamide (3AB). 3AB inhibits the synthesis of poly(ADP-ribose) by the enzyme adenosine diphosphate ribosyl transferase (ADPRT), which requires NAD as a substrate. 3AB also prevents chromosomal repair, as measured in X-ray dose-fractionation studies. Because 3AB might interfere with metabolic reactions other than those mediated by ADPRT, experiments were carried out to see if the adaptive response was also inhibited in nicotinamide-free medium, which prevents poly(ADP-ribosyl)ation by depleting cellular NAD. The experiments show that the incorporation of (/sup 3/H)dThd has no effect on the induction of chromosomal aberrations by subsequent doses of X rays if the cells are cultured in nicotinamide-free medium. Nicotinamide deficiency mimics the effects of 3AB on both the adaptive response and chromosome repair. The results indicate that ADPRT activity itself, and not other metabolic processes affected by inhibitors of this enzyme, plays an essential role in the adaptive response.

• Research Organization: Univ. of California, San Francisco
• OSTI ID: 6064892
• Journal Information: Exp. Cell Res.; (United States), Vol. 171:2
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CHROMOSOMAL ABERRATIONS
RADIOINDUCTION
LYMPHOCYTES
DNA REPAIR
GENETIC RADIATION EFFECTS
NICOTINAMIDE
RADIOSENSITIVITY EFFECTS
ADP
BIOLOGICAL ADAPTATION
CELL CULTURES
DNA
ENZYME INHIBITORS
FRACTIONATED IRRADIATION
INHIBITION
MAN
NAD
RIBOSE
THYMIDINE
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
X RADIATION
ALDEHYDES
AMIDES
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
COENZYMES
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
ENZYMES
GENETIC EFFECTS
HETEROCYCLIC COMPOUNDS
IONIZING RADIATIONS
IRRADIATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
MAMMALS
MATERIALS
MONOSACCHARIDES
MUTATIONS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PENTOSES
PRIMATES
PYRIDINES
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RECOVERY
REPAIR
RIBOSIDES
SACCHARIDES
SOMATIC CELLS
VERTEBRATES
VITAMIN B GROUP
VITAMINS
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture