Carcinogenesis, Vol 19, 623-629, Copyright © 1998 by Oxford University Press
TC Wang, JM Chiou, YL Chang and MC Hu
N-Nitroso propoxur (NP) can be synthesized from a widely used N-
methylcarbamate insecticide, propoxur, in vitro in the laboratory. Because
of the extensive use of aerosol propoxur, the adverse effect on cells of
respiratory origin is worth elucidating. In this report, two mammalian cell
cultures from respiratory tissues [a hamster lung fibroblast, V79, and a
primary rat tracheal epithelial cell (RTE)], were used to investigate the
genotoxicity of propoxur and NP. NP was more cytotoxic than propoxur, with
LC50s (20 and six times smaller, respectively in V79 and RTE cells. NP
significantly induced sister chromatid exchange (> or = 0.01 microg/ml),
chromosome aberration (> or = 2.5 microg/ml) and hprt gene mutation
(> or = 0.5 microg/ml) in V79 cells, and cell transformation (> or =
0.2 microg/ml) in RTE cells. Results of chromosome aberration and hprt gene
mutation indicated that the major pre-mutagenic lesion induced by NP must
be the O6- methylguanine adduct, which frequently mispairs with thymine and
thus gives rise to a GC-->AT transition. Propoxur was not mutagenic to
either type of cells. However, it inhibited gap-junctional intercellular
communication in V79 cells, which indicates that propoxur could act through
some epigenetic mechanisms, such as tumor promotion or cell proliferation,
in the multiple process of chemical carcinogenesis.
ARTICLES
Genotoxicity of propoxur and its N-nitroso derivative in mammalian cells
Institute of Zoology, Academia Sinica, Taipei, Taiwan. tcwang@sinica.edu.tw
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