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 language | English |
|---|---|
| Pages (from-to) | 163-168 |
| Number of pages | 6 |
| Journal | Mutation Research Letters |
| Volume | 348 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1995 |
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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 journal › Article
}
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 -