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ToxSci Advance Access originally published online on March 25, 2003
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Toxicological Sciences 73, 114-123 (2003)
Copyright © 2003 by the Society of Toxicology

MOLECULAR AND GENETIC TOXICOLOGY

Genotoxicity of Samples of Nickel Refinery Dust

Farrah Clemens*,{dagger} and Joseph R. Landolph*,{dagger},{ddagger},§,1

* Department of Molecular Microbiology and Immunology, {dagger} USC/Norris Comprehensive Cancer Center, and {ddagger} Department of Pathology, Keck School of Medicine; and § Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, California 90033

At the International Nickel Company (INCO) nickel refinery in Clydach, Wales, U.K., which has operated since 1901, 365 respiratory cancers, including 85 nasal cancers and 280 lung cancers, have occurred in workers since the 1920s. From 1901 to 1923, incidences of these cancers were high. In 1923, the refining process was changed, eliminating a nickel arsenide, Ni5As2, called orcelite, from the refinery. Incidences of respiratory cancers decreased substantially from 1925 to 1930. Refinery dust samples were obtained in 1920 and in 1929; both of these samples contain primarily nickel oxide (NiO), but the 1920 sample also contains orcelite. The orcelite content of the 1920 sample is ~10%, while that of the 1929 sample is ~1%. We hypothesized that orcelite in the 1920 sample was partially responsible for inducing nasal and lung cancers in the refinery workers, and we tested this hypothesis. The 1920 and 1929 samples and orcelite were phagocytosed by cultured C3H/10T1/2 Cl 8 (10T1/2) mouse embryo cells to similar extents and were similarly cytotoxic to 10T1/2 cells. The 1920 sample and orcelite induced dose-dependent morphological transformation of 10T1/2 cells; the 1929 sample did not. The cell transforming ability of the 1920 sample, and therefore its probable carcinogenicity, correlates with induction of respiratory cancers in refinery workers exposed to orcelite-containing nickel refinery dust before 1923. Inability of the 1929 sample to induce morphological transformation correlates with decreased human respiratory tumor incidence at this plant after 1923. This data supports our hypothesis that orcelite in the 1920 refinery sample contributed to its carcinogenicity to nickel refinery workers.

Key Words: orcelite; nickel arsenide; morphological cell transformation; C3H/10T1/2 mouse embryo cells; green (high-temperature) nickel oxide.


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