Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro.
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 single 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.
Graduate School of Natural Science and Technology, Okayama University, Japan.
Y
Y
Yamashita
N
N
Sumi
S
S
Arimoto
H
H
Hayatsu
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001711:Biotransformation; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D003640:Dealkylation; D004052:Diethylnitrosamine / Q000528:radiation effects / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D009153:Mutagens / Q000528:radiation effects / Q000633:toxicity*; D009242:N-Nitrosopyrrolidine / Q000528:radiation effects / Q000633:toxicity; D009602:Nitrosamines / Q000528:radiation effects / Q000633:toxicity*; D009603:Nitroso Compounds / Q000528:radiation effects / Q000633:toxicity; D010777:Photochemistry; D013481:Superoxides / Q000633:toxicity*; D014466:Ultraviolet Rays
D000975:Antioxidants; D009153:Mutagens; D009602:Nitrosamines; D009603:Nitroso Compounds; D013481:Superoxides; C008651:4-nitrosodimethylaniline; D004052:Diethylnitrosamine; C002741:N-nitrosomorpholine; C002743:N-nitrosopiperidine; D009242:N-Nitrosopyrrolidine