Genetic Effects Induced by Nickel Sulfate in Germline and Somatic Cells of WR Mice

ISSN： 1022-7954

Source： Russian Journal of Genetics, Vol.41, Iss.7, 2005-07, pp. : 728-734

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Abstract

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (1/200–1/20 LD₅₀) on the frequency of dominant lethal mutations and double-strand DNA breaks (DSBs) in germline cells and on an increase in frequency in gene mutations W ^y in pigment cells of first-generation mice. The results indicated that spermatogenesis stages most sensitive to nickel sulfate (at a dose of 1.0 mg/kg) are spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia. No statistically significant increase in the total TSB level was detected in spermatozoids 4 weeks after exposure. At the same time, a significant (P < 0.05) increase in percentage of cells with an extremely high level of DNA fragmentation (supposedly apoptotic cells) was observed upon exposure at a dose of 0.5 mg/kg. Nickel sulfate at doses of 5.0 and 1.0 mg/kg induced a marked increase in the c-kit gene expression in pigment cells of heterozygous first-generation WR mice as compared to control (P < 0.001). It was shown that the nonobservable adverse effect level (NOAEL) of nickel sulfate on the dominant lethal mutation frequency and gene mutations was 1/200 LD₅₀, while the lowest observable adverse effect level (LOAEL) was 1/100 LD₅₀.