Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats.
Chemopreventive effects of arctiin, a lignan isolated from Arctium lappa (burdock) seeds, on the initiation or post initiation period of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced mammary carcinogenesis in female rats and on 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-associated hepatocarcinogenesis in male rats were examined. In experiment 1, female Sprague-Dawley (SD) rats were given intragastric doses of 100 mg/kg body wt of PhIP once a week for 8 weeks as initiation. Groups of 20 rats each were treated with 0.2 or 0.02% arctiin during or after PhIP initiation. Control rats were fed 0.2 or 0.02% arctiin, or basal diet alone during the experimental period. Animals were killed at the end of week 48. Although the incidence of mammary carcinomas did not significantly differ among the PhIP-treated groups, multiplicity was significantly decreased in rats given 0.2 (0.7+/-0.7, P<0.05) or 0.02% (1.0+/-1.1, P<0.05) arctiin after PhIP initiation as compared with the PhIP alone controls (2.1+/-2.5). The average number of colon aberrant crypt foci was also significantly decreased in these two groups. Pancreas acidophilic foci were induced in PhIP treated animals with slight decrease in the multiplicity with arctiin during the initiation phase. For liver carcinogenesis, groups of 15 male F344 rats were given a single intraperitoneal injection of diethylnitrosamine (DEN) and starting 2 weeks later, they were administered 0.03% MeIQx in the diet, MeIQx together with 0.5% arctiin, 0.1% arctiin or basal diet for 6 weeks. They were subjected to two-third partial hepatectomy 3 weeks after DEN initiation and killed at the end of week 8 for glutathione S-transferase placental form (GST-P) immunohistochemistry. The numbers and areas of preneoplastic GST-P positive foci were elevated by the treatment with MeIQx, and further increased by the simultaneous treatment with arctiin. These results indicate that arctiin has a protective effect on PhIP-induced carcinogenesis particularly in the mammary gland in the promotion period. On the other hand, it may have a weak co-carcinogenic influence on MeIQx-induced hepatocarcinogenesis. In addition, the results suggested that PhIP is a weak pancreatic carcinogen in female SD rats, targeting acinar cells.
Hirose
M
M
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. m-hirose@nihs.go.jp
Yamaguchi
T
T
Lin
C
C
Kimoto
N
N
Futakuchi
M
M
Kono
T
T
Nishibe
S
S
Shirai
T
T
D000818:Animals; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004032:Diet; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D018226:Fibroadenoma / Q000139:chemically induced; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007093:Imidazoles; D008099:Liver / Q000187:drug effects; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D011810:Quinoxalines; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002273:Carcinogens; D004365:Drugs, Chinese Herbal; D005663:Furans; D005960:Glucosides; D007093:Imidazoles; D011810:Quinoxalines; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D005982:Glutathione Transferase; C077992:arctiin; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine