Carcinogenesis, Vol 19, 1783-1788, Copyright © 1998 by Oxford University Press
JG Rosa, B Prokopczyk, DH Desai, SG Amin and K El-Bayoumy
1,4-Phenylenebis(methylene)selenocyanate (p-XSC) is an effective
chemopreventive agent against 4-(methylnitrosamino)-1-(3-pyridyl)-1-
butanone (NNK)-induced lung adenoma in female A/J mice. While p-XSC can
effectively inhibit NNK-induced DNA methylation in female A/J mice and in
male F344 rats, its effect on NNK-induced oxidative DNA damage had not been
determined. Thus, the effect of p-XSC on the levels of 8-
hydroxy-2'-deoxyguanosine (8-OH-dG) in lung DNA from A/J mice and F344 rats
treated with NNK was examined. Mice were given NNK by gavage (0.5 mg/mouse
in 0.2 ml corn oil, three times per week for 3 weeks) or by a single i.p.
injection (2 mg/mouse in 0.1 ml saline) while maintained on a control diet
(AIN-76A) or control diet containing p-XSC at 10 or 15 p.p.m. (as Se)
starting 1 week before NNK administration and continuing until termination.
Mice were killed 2 h after the last NNK gavage in the multiple
administration protocol or 2 h after the single i.p. injection. Treatment
with NNK by gavage significantly elevated the levels of 8-OH-dG in lung DNA
of A/J mice from 0.7 +/- 0.1 to 1.6 +/- 0.2 adducts/10(5) 2'-deoxyguanosine
(dG) (P < 0.001), while dietary p- XSC (at 10 p.p.m. Se) prevented
significant elevation of the levels of this lesion caused by NNK, keeping
them at 0.9 +/- 0.1 adducts/10(5) dG (P < 0.003). Injection of NNK in
saline also significantly increased the levels of 8-OH-dG in lung DNA of
A/J mice from 1.2 +/- 0.6 to 3.6 +/- 0.8/10(5) dG adducts (P < 0.01),
while dietary p-XSC (at 15 p.p.m. Se) kept these levels at 1.9 +/- 0.5
adducts/10(5) dG (P < 0.03). Rats were given a single i.p. injection of
NNK (100 mg/kg body wt) in saline while being maintained on control diet
(AIN-76A) or control diet containing p-XSC (15 p.p.m. as Se) starting 1
week before NNK administration and continuing until termination. The rats
were killed 2 h after injection. Treatment with NNK using this protocol
significantly elevated the levels of 8-OH-dG in lung DNA of F344 rats from
2.6 +/- 0.5 to 3.5 +/- 0.5 adducts/10(5) dG (P < 0.03), while dietary
p-XSC (at 15 p.p.m. Se) kept the levels of this lesion at 2.2 +/- 0.6
adducts/10(5) dG (P < 0.01). Our findings suggest that the
chemopreventive efficacy of p-XSC against NNK-induced lung tumorigenesis in
A/J mice and F344 rats may be due in part to inhibition of oxidative DNA
damage.
ARTICLES
Elevated 8-hydroxy-2'-deoxyguanosine levels in lung DNA of A/J mice and F344 rats treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and inhibition by dietary 1,4-phenylenebis(methylene)selenocyanate
American Health Foundation, Valhalla, NY 10595, USA.
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