Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II)carcinogenesis
K. Bialkowski et al., Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II)carcinogenesis, CARCINOGENE, 20(8), 1999, pp. 1621-1624
8-Oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase
) is an enzyme which prevents incorporation into DNA of promutagenic 8-oxo-
2'-deoxyguanosine (8-oxo-dG) from a deoxynucleotide pool damaged by endogen
ous oxidants, Its inhibition may thus be carcinogenic. We previously found
that Cd(II) inhibited 8-oxo-dGTPase in both cell free systems and cultured
cells. To verify this finding in a relevant animal model, we investigated t
he effects of Cd(II) on cellular 8-oxo-dGTPase activity and nuclear DNA 8-o
xo-dG levels in the rat testis, a target organ for Cd(II) carcinogenesis. N
i(II), which does not induce testicular tumors in rats and is a weaker in v
itro inhibitor of 8-oxo-dGTPase than Cd(II), was investigated as a comparis
on. Male F344/NCr rats were given a single s.c. dose of 20 mu mol Cd(II) ac
etate, 90 mu mol Ni(II) acetate or 180 mu mol sodium acetate (controls) per
kg body wt and killed 2, 8, 24 or 48 h later (three rats/time point). Cd(I
I) caused a gradual decrease in testicular 8-oxo-dGTPase activity with time
. It became significant only after 8 h postinjection (P < 0.05) and resulte
d in a final 50% loss of the enzyme activity at 48 h (P < 0.01). Although t
he results for Ni(II) at 8 h and later were apparently lower than the contr
ols, the decrease did not reach statistical significance, Treatment of rats
with Cd(II) led to an early and progressive increase (from 130% at 2 h to
200% at 48 h versus the controls) of the 8-oxo-dG level in testicular DNA (
P < 0.05 or better). NI(II) acetate also tended to raise the testicular 8-o
xo-dG level, but the increase was transient, with an apparent maximum at 8
h, and did not approach statistical significance (P < 0.2), Thus, Cd(II), u
nlike Ni(II), is able to inhibit 8-oxo-dGTPase activity and to raise 8-oxo-
dG levels in rat testicular DNA, However, the time course of both effects i
ndicates that 8-oxo-dGTPase inhibition is most likely not the sole cause of
the increase in 8-oxo-dG.