Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro

Yasuhiro Yamashita, Nabuyoshi Sumi, Sakae Arimoto, Hikoya Hayatsu

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7 Citations (Scopus)

Abstract

N-Nitrosodialkylamines are promutagens and proclastogens, requiring metabolic activation for their actions. Previously, we showed that direct-acting bacterial mutagens can be formed from N-nitrosodialkylamines on exposure to near-UV. We have now found that N-nitrosodialkylamines with near-UV irradiation are clastogenic to Chinese hamster lung cells. When the cells in culture were irradiated with near-UV for 3 h in the presence of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP) or N-nitrosomorpholine (NMOR), and then further incubated for a total period of 24 h with the N-nitrosodialkylamines, chromosome aberrations were induced. Neither the N-nitrosodialkylamine nor near-UV alone were clastogenic. Severe clastogenicity (> 50% of cells examined showing aberrations) was observed for 0.5 mM NDEA, NPYR and NPIP. The order of the clastogenic activity was NDEA, NPYR > NPIP, NDMA > NMOR. This order differed from that of bacterial mutagenicity previously reported for these N-nitrosodialkylamines plus near-UV, in which NMOR gave the strongest activity. The chromosome aberrations induced by the NPYR and NDEA plus near-UV in CHL-cells were inhibited by superoxide dismutase, glutathione and l-cysteine. Dimethylsulfoxide or d-mannitol, scavengers of hydroxy radical, and l-histidine, a scavenger of singlet oxygen, were ineffective. These results suggest that superoxide formed by a synergistic action of an N-nitrosodialkylamine and near-UV is the cause of the chromosome aberrations observed, an assumption consistent with the known ability of superoxide to cleave DNA.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalMutation Research Letters
Volume348
Issue number4
DOIs
Publication statusPublished - Dec 1995

Keywords

  • Active-oxygen radical scavenger
  • Chromosome aberration
  • N-Nitrosodialkylamine
  • Near-UV
  • Superoxide
  • Synergistic action

ASJC Scopus subject areas

  • Medicine(all)

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