Effects of dietary administration of
1'-acetoxychavicol acetate (ACA) and the novel synthetic
retinoids 4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]
benzoic acid (
Re-80); 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]
benzoic acid (
Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]
nicotinic acid (Am-55P) were examined using a two-stage rat
carcinogenesis model. A total of 190 female SD rats was treated sequentially with
1,2-dimethylhydrazine (
DMH, s.c.);
7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and
2,2'-dihydroxy-di-n-propylnitrosamine (
DHPN, in the
drinking water) during the first three weeks (
DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated
Re-80 (at dose levels of 1.0 or 0.4 ppm),
Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm),
all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After
DDD-initiation,
all-trans-retinoic acid at the high dose delayed the development of mammary
tumors. The multiplicity of colon
tumors in the group fed Am-55P and the incidences of
nephroblastomas with ACA or
Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on
tumor development in any organs. Thus, among ACA and the novel synthetic
retinoids tested, only Am-55P showed a weak inhibitory effect on a
neoplasm of general interest under the present experimental conditions.