We have previously generatedconvincing evidence that combinations of
N
-acetyl-
S
-(
N
-2-phenethylthiocarbamoyl)-L-cysteine
(PEITC-NAC, 3 μmol/g diet) and
myo
-inositol (MI, 56
μmol/g diet) were ...significantly more effective than the individual
compounds as inhibitors of tobacco smoke carcinogen-induced lung tumorigenesis
in A/J mice. In this study, we further investigated the efficacy of combinations
of PEITC-NAC (9 or 15 μmol/g diet) and MI (56 μmol/g diet).
Female A/J mice were treated with a mixture of the tobacco smoke carcinogens
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and
benzo
a
pyrene (BaP) by gavage once weekly
for eight weeks. PEITC-NAC plus MI was given in the diet beginning at one day
after the 4
th
of eight carcinogen treatments (temporal sequence A) or
one week after the last carcinogen treatment (temporal sequence B). Regardless
of the dose of carcinogen or PEITC-NAC plus MI, or temporal sequence,
administration of PEITC-NAC plus MI significantly reduced the multiplicity of
gross tumors and, in most instances, adenocarcinoma. PEITC-NAC plus MI was
particularly effective against bigger tumors. The observed inhibition of lung
tumorigenesis by PEITC-NAC plus MI was attributed, at least partly, to
inhibition of cell proliferation and induction of apoptosis. These results
clearly demonstrate the efficacy of PEITC-NAC plus MI in the prevention of
tobacco carcinogen-induced lung adenocarcinoma in A/J mice and provide a basis
for future evaluation of PEITC-NAC plus MI in clinical trials as a
chemopreventive agent for current and former smokers.
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