Ks. Kasprzak et K. Bialkowski, Inhibition of antimutagenic enzymes, 8-oxo-dGTPases, by carcinogenic metals. Recent developments, J INORG BIO, 79(1-4), 2000, pp. 231-236
Nickel, cadmium, cobalt, and copper are carcinogenic to humans and/or anima
ls, but the underlying mechanisms are poorly understood. Our studies have b
een focused on one such mechanism involving mediation by the metals of prom
utagenic oxidative damage to DNA bases. The damage may be inflicted directl
y in DNA or in the deoxynucleotide pool, from which the damaged bases are i
ncorporated into DNA. Such incorporation is prevented in cells by 8-oxo-2'-
deoxyguanosine 5'-triphosphate pyrophosphatases (8-oxo-dGTPases). Thus, inh
ibition of these enzymes should enhance carcinogenesis. We have studied eff
ects of Cd(II), Cu(II), Co(II), and Ni(II) on the activity of isolated bact
erial and human 8oxo-dGTPases. Cd(II) and Cu(II) were strongly inhibitory,
while Ni(II) and Co(II) were much less suppressive. After developing an ass
ay for 8-oxo-dGTPase activity, we confirmed the inhibition by Cd(II) in cul
tured cells and in the rat testis, the target organ for cadmium carcinogene
sis. 8Oxo-dGTPase inhibition was accompanied by an increase in the g-oxo-dG
level in testicular DNA. (C) 2000 Elsevier Science Inc. All rights reserve
d.