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

Research output: Contribution to journalArticle

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 - 1995

Fingerprint

N-nitrosopiperidine
Diethylnitrosamine
Fibroblasts
Chromosomes
Cricetulus
Aberrations
Chromosome Aberrations
Dimethylnitrosamine
Lung
Superoxides
N-Nitrosopyrrolidine
Singlet Oxygen
Mutagens
Mannitol
Dimethyl Sulfoxide
Histidine
Superoxide Dismutase
Glutathione
Cysteine
Cell Culture Techniques

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Toxicology

Cite this

Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro. / Yamashita, Yasuhiro; Sumi, Nabuyoshi; Arimoto, Sakae; Hayatsu, Hikoya.

In: Mutation Research Letters, Vol. 348, No. 4, 1995, p. 163-168.

Research output: Contribution to journalArticle

@article{831430cb248c4538a14574494865d111,
title = "Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro",
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.",
keywords = "Active-oxygen radical scavenger, Chromosome aberration, N-Nitrosodialkylamine, Near-UV, Superoxide, Synergistic action",
author = "Yasuhiro Yamashita and Nabuyoshi Sumi and Sakae Arimoto and Hikoya Hayatsu",
year = "1995",
doi = "10.1016/0165-7992(95)90004-7",
language = "English",
volume = "348",
pages = "163--168",
journal = "Mutation Research Letters",
issn = "0165-7992",
publisher = "Elsevier BV",
number = "4",

}

TY - JOUR

T1 - Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro

AU - Yamashita, Yasuhiro

AU - Sumi, Nabuyoshi

AU - Arimoto, Sakae

AU - Hayatsu, Hikoya

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - Active-oxygen radical scavenger

KW - Chromosome aberration

KW - N-Nitrosodialkylamine

KW - Near-UV

KW - Superoxide

KW - Synergistic action

UR - http://www.scopus.com/inward/record.url?scp=0029417307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029417307&partnerID=8YFLogxK

U2 - 10.1016/0165-7992(95)90004-7

DO - 10.1016/0165-7992(95)90004-7

M3 - Article

C2 - 8544868

AN - SCOPUS:0029417307

VL - 348

SP - 163

EP - 168

JO - Mutation Research Letters

JF - Mutation Research Letters

SN - 0165-7992

IS - 4

ER -