Genotoxicity of low dose N-nitroso propoxur to human gastric cells.
Propoxur is among the most popular insect control agents in subtropical countries such as Taiwan. As a member of the N-methylcarbamate insecticide group, propoxur is notorious for its potential for conversion into highly genotoxic N-nitroso derivatives. Due to the fact that the stomach has been identified as the major target for N-nitroso N-methylcarbamates, this investigation used a human gastric cell line, SC-M1, in order to obtain results pertinent to the authentic adverse effects of this compound on human health. This report reveals that at dose levels inhibiting < or = 10% cell growth, a 2-h pulsed treatment of N-nitroso propoxur induced significant amounts of DNA damage. Most of the damaged DNA was repaired within 24 h after treatment removal, such that an outcome with a significant induction of chromosomal aberrations was not observed. Gene mutations and anchorage independence, on the other hand, were significantly induced by this same treatment. In conclusion, exposure to low doses of N-nitroso propoxur is not cytotoxic nor clastogenic, nevertheless, has the potential to increase genetic instability and, possibly as a result, to enhance the malignant potential of treated cells. We suggest that although the damaged DNA was repaired during the transient G2/M arrest period, it was probably not done in an appropriate way which would preserve the original genetic stability.
Kuo
H H
HH
Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei, Taiwan.
Shyu
S S
SS
Wang
T C
TC
D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000378:metabolism*; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007306:Insecticides / Q000633:toxicity; D007700:Kinetics; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D001074:Propoxur / Q000031:analogs & derivatives* / Q000633:toxicity; D013270:Stomach / Q000166:cytology; D014466:Ultraviolet Rays
C468783:H2AX protein, human; D006657:Histones; D007306:Insecticides; D009153:Mutagens; C063383:N-nitrosopropoxur; D001074:Propoxur; D007041:Hypoxanthine Phosphoribosyltransferase