Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream
smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice and lung
tumor count. Male animals were fed either 0.2%
N-acetylcysteine (NAC) or 0.05%
phenethyl isothiocyanate (
PEITC) in diet AIN-76A with 5%
corn oil added. Female animals received normal laboratory chow and were given a 1.25% extract of
green tea in the
drinking water. Corresponding control groups were fed diets without NAC or
PEITC or given plain tap water. Exposure to tobacco
smoke increased lung
tumor multiplicity to 1.1-1.6
tumors/lung, significantly higher than control values (0.5-1.0
tumors/lung). None of the putative chemopreventive agents (NAC,
PEITC or
green tea extract) had a protective effect. In positive control experiments,
PEITC significantly reduced both lung
tumor multiplicity and incidence in mice treated with the tobacco
smoke-specific
carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In mice treated with three different doses of
urethan and fed NAC in the diet, a significant reduction in lung
tumor multiplicity was found only at one dose level.
Green tea extract did not reduce lung
tumor multiplicity in animals treated with a single dose of NNK. It was concluded that successful
chemoprevention of tobacco
smoke-induced lung
tumorigenesis might require administration of several chemopreventive agents rather than just a single one.