Nicotinamide Starvation and Inhibition of Poly (ADP-Ribose) Synthesis Enhance the Induced Mutation in Chinese Hamster V79 Cells

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概要

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• The effects of nicotinamide (NA) deficiency and added NA and 3-aminobenzarnide (3AB) on the cytotoxicity and the induction of mutations in Chinese hamster V79-14 cells were investigated. In NA deficiency the addition of NA (up to 4 mM) and 3AB (up to 7.5 mM) was not cytotoxic. The presence of NA prior to exposure to mitomycin C (MMC) or γ-rays produced a dose-dependent increase in the relative cloning ability of DNA-damaged cells. The lethality of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was significantly potentiated by pre-treatment with 5 mM 3AB, but no potentiation by 3AB was observed for MMC, ultraviolet (UV)-B light, or γ-rays. Among cells pre-cultured in NA-free medium there were increased frequencies of mutations at both the hypoxanthineguanine phosphoribosyltransferase (HGPRT) and the adenine phosphoribosyltransferase (APRT) loci following DNA damage. The enhancing effect by NA deficiency was time-dependent. Incubation with NA prior to DNA damage produced a significant reduction in the frequency of mutations. The addition of 3AB to the nicotinamide adenine dinucleotide (NAD^+)-depleted cell cultures before or after the DNA damage also strongly increased the frequency of induced mutations, with increasing concentrations of 3AB up to 5 mM, but the frequency was reduced at higher concentrations. The interaction between NA deficiency and the addition of 3AB appears to act synergistically on mutation induction. A correlation was observed between the potential of inhibiting poly (ADP-ribose) polymerase and the enhancement of mutation frequency.

• 日本放射線影響学会の論文

著者

• Okada G

  Inst. Physical And Chemical Research(riken) Saitama Jpn

• KANEKO Ichiro

  RIKEN (The Institute of Physics and Chemical Research)

• KANEKO ICHIRO

  Radiation Biology Laboratory, Institute of Physical and Chemical Research

• Okada Gensaku

  Radiation Biology Laboratory The Institute Of Physical And Chemical Research

• Mitsui Hideki

  Predoctoral Student In The Department Of Veterinary Radiology Nihon University

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• Induction of Non-repairable DNA Strand Breaks by N-ion Beams
• Nicotinamide Starvation and Inhibition of Poly (ADP-Ribose) Synthesis Enhance the Induced Mutation in Chinese Hamster V79 Cells

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