Authors
Tsuda H. Iwahori Y. Asamoto M. Baba-Toriyama H. Hori T. Kim DJ. Uehara
N. Iigo M. Takasuka N. Murakoshi M. Nishino H. Kakizoe
T. Araki E. Yazawa K.
Institution
National Cancer Center Research Institute, National Cancer Center Hospital,
Tokyo, Japan.
Title
Demonstration of organotropic effects of chemopreventive agents in multiorgan
carcinogenesis models.
Source
IARC Scientific Publications. (139):143-50, 1996.
Abstract
Organotropic chemopreventive effects of three (pro)vitamins and three
unsaturated fatty acids were examined using mouse and rat multiorgan
carcinogenesis models. For the study of (pro)vitamins, male and female B6C3F1
mice were treated with N,N-diethylnitrosamine (DEN) and
N-methyl-N-nitrosourea (MNU) during the first 11 weeks, then from weeks 12 to
32 they received alpha-carotene (0.4 mg/mouse), beta-carotene (0.4 mg/mouse)
or alpha-tocopherol (40 mg/mouse) three times a week by gavage; control mice
received vehicle alone. In male mice, alpha-carotene significantly reduced
liver weights, representing a reduced tumour mass (P < 0.001), and
alpha-carotene, beta-carotene and alpha-tocopherol significantly reduced the
numbers of liver tumours (adenomas and carcinomas combined) (P < 0.001-0.01)
as compared with control mice, the effects being greatest with
alpha-carotene. In female mice, alpha-carotene significantly decreased the
number of liver tumours (P < 0.001). In the lung, alpha-carotene and
alpha-tocopherol reduced the area of lesions (hyperplasias and adenomas
combined) only in males (P < 0.05). For the study of unsaturated fatty acids,
F344 male rats were treated with DEN, MNU, N-butyl-N-hydroxybutylnitrosamine
(BBN), 1,2-dimethylhydrazine (DMH) and N,N-bis(2-hydroxy)propylnitrosamine
during the first 5 weeks, then from weeks 6 to 36 they were given
docosahexaenoic acid (C22:6), eicosapentaenoic acid (C20:5) or linoleic acid
(C18:2) at 1.0 g/rat, three times a week by gavage; control rats were treated
with oleic acid (C18:1) using the same protocol. All animals were fed a low
linoleic acid and calorie-adjusted basal diet during fatty acid
administration. Docosahexaenoic acid and linoleic acid reduced tumours in the
large and small intestines, respectively. However, they did not influence the
yield of preneoplastic liver, lung, kidney, forestomach and urinary bladder
lesions. The data thus provide evidence for organotropic effects of
carotenoids and unsaturated fatty acids on carcinogenesis.