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

Abstract

We examined the effects of nickel sulfate at doses 0.5 to 5.0 mg/kg (1/200-1/20 LD 50 ) 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 LD 50 , while the lowest observable adverse effect level (LOAEL) was

Nickel Toxicity and Carcinogenesis

“…Subcutaneous injections of nickel sulfate to rats caused hyperemia of testicular intertubullar capillaries, disintegration of spermatozoa, and inhibition of spermatogenesis, depending on the dose [141,142]. Domshlak et al [143] found that in mice spermatozoids, early spermatids, late spermatocytes, and stem spermatogonia are most sensitive to nickel sulfate. On the other hand, nickel deprivation also reduced the rat reproductive performance by decreasing sperm production rate and spermatozoa motility.…”

Hystometric evaluation of nickel chronic exposure effects on large instestine of adult Wistar male rats

“…Some researchers and toxicologists are focusing on the risk of environmental pollution by heavy metals, which are dangerous and cause effects related to animal studies, toxic effects due to oral exposure, with the possibility of slow development (Domshlak et al, 2005).…”

Effect of Nickel on Male Reproduction

“…These findings suggest that testicular toxicity of nickel compounds may be related to enhanced production of reactive oxygen species, probably mediated through oxidative damage to macromolecules, including damage of DNA. Lindemann et al [11] investigated a selective effect of Ni 2+ on wave initiation in bull spermatozoa flagella. Although spontaneous coordination of flagellum waves is lost after exposure to Ni 2+ , other function of the flagellum remain intact.…”