Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model.
The effects of cacao liquor proanthocyanidins (CLPr) on tumorigenesis were investigated using a multi-organ carcinogenesis model in male F344 rats receiving combined treatment with a single i.p. injection of diethylnitrosamine (100 mg/kg body wt), four i.p. injections of N-methylnitrosourea (20 mg/kg body wt), four s.c. injections of dimethylhydrazine (40 mg/kg body wt), along with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and then 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine, both in the drinking water, for 2 weeks each, during the initial 4-week period (DMBDD treatment). Starting 1 week thereafter, rats were administered CLPr at a dose of 0.025% or 0.25% and the experiment was terminated at week 36. The final survival rate for the DMBDD+0.25% CLPr group was significantly greater than for the DMBDD alone group. In the lung, significant reduction in the incidence and multiplicity of carcinomas was also observed, and in the thyroid, quantitative values for adenomas also tended to decrease in a CLPr dose-dependent manner. No significant modification in the small intestine, colon or kidney was evident. These results indicate that CLPr exerts chemopreventive effects in the lung without any promoting influence in other major organs.
Yamagishi
Megumi
M
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Natsume
Midori
M
Osakabe
Naomi
N
Okazaki
Kazushi
K
Furukawa
Fumio
F
Imazawa
Takayoshi
T
Nishikawa
Akiyoshi
A
Hirose
Masao
M
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D002099:Cacao / Q000737:chemistry*; D002277:Carcinoma / Q000139:chemically induced / Q000517:prevention & control; D002392:Catechin / Q000032:analysis / Q000494:pharmacology; D004052:Diethylnitrosamine / Q000633:toxicity; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D009602:Nitrosamines / Q000633:toxicity; D009928:Organ Specificity; D010636:Phenols / Q000032:analysis / Q000494:pharmacology; D008517:Phytotherapy; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use*; D011108:Polymers / Q000032:analysis / Q000494:pharmacology; D044945:Proanthocyanidins; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D014565:Urogenital Neoplasms / Q000139:chemically induced / Q000517:prevention & control
D000872:Anthocyanins; D016588:Anticarcinogenic Agents; D005419:Flavonoids; D009602:Nitrosamines; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D044945:Proanthocyanidins; C013221:proanthocyanidin; D002085:Butylhydroxybutylnitrosamine; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; D008770:Methylnitrosourea; D002392:Catechin; D019813:1,2-Dimethylhydrazine