fumonisin-b1 and Papilloma

An extract of the roots of Taraxacum japonicum (Compositae) exhibited strong anti-tumor-promoting activities on the two-stage carcinogenesis of mouse skin tumor induced by dimethylbenz[a] anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter, as well as on that induced by DMBA and fumonisin B1. Further, the extract exhibited anti-tumor-initiating activity on the two-stage carcinogenesis of mouse skin tumor induced by (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexen amide (NOR-1) as an initiator and TPA as a promoter. These results suggested that an extract of the roots of the Taraxacum plant could be a valuable chemopreventive agent against chemical carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Carboxylic Acids; Female; Fumonisins; Humans; Mice; Mice, Inbred ICR; Papilloma; Plant Extracts; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate

Seven saponins (1-7) isolated from the rhizomes and roots of Panax vietnamensis were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells as a primary screening test for anti-tumor-promoters (cancer chemopreventive agents). The ocotillol-type saponin, majonoside-R2 (2), which is the major and characteristic constituent of this plant, exhibited a significant inhibitory effect on EBV-EA activation. Furthermore, the cell cycle analysis of 2 on Raji cells was also examined and strong inhibition was observed on the effect of the cell cycle induced by TPA. Compound 2 showed potent anti-tumor-promoting activity in two-stage carcinogenesis tests of mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA or fumonisin B1 as a promoter. Consequently, these results suggest that majonoside-R2 (2) could be a valuable chemopreventive agent against chemical carcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Antigens, Viral; Carboxylic Acids; Fumonisins; Ginsenosides; Male; Mice; Mice, Inbred ICR; Papilloma; Saponins; Skin Neoplasms; Tetradecanoylphorbol Acetate

Fumonisins and N-nitrosamines (NNO) are suggested risk factors in the development of human oesophageal cancer; exposure to both occurs in high risk populations in Africa and People's Republic of China. The hypothesis that the two would interact in oesophageal carcinogenesis was therefore tested by treating male rats with the known oesophageal carcinogen N-methylbenzylnitrosamine (NMBA), and fumonisin B1 (FB1). The treatment groups were: Group 1, NMBA (2.5 mg/kg) intraperitoneally twice per week from week 2 to 4 inclusive; Group 2, as for group 1 but in addition FB1 (5 mg/kg) daily from weeks 1 to 5 inclusive by gavage; Group 3, FB1 (5 mg/kg) alone daily from weeks 1 to 5 inclusive by gavage, and Group 4, vehicle treatment from week 1 to 5 inclusive. Two of 12 animals in group 1 developed oesophageal papillomas and a further two had oesophageal dysplasia. Data were similar in group 2, animals receiving both NMBA and FB1, with one of 12 animals having papillomas and three of 12 with dysplasia. Sphingolipid biosynthesis was affected in the kidney and slightly in the liver after fumonisin treatment but not in the oesophagus or lung as determined by sphinganine:sphingosine ratios in urine and tissues. These data show that there is no synergistic interaction between NMBA and FB1 in the rat oesophagus when the two compounds are administered together. It is nevertheless important to examine other experimental models and treatment protocols which may be more relevant to the human situation and also to pursue epidemiological investigations of the role of fumonisins in oesophageal cancer.

Topics: Animals; Carboxylic Acids; Carcinogens; Cocarcinogenesis; Dimethylnitrosamine; Drug Synergism; Esophageal Neoplasms; Fumonisins; Infusions, Parenteral; Male; Papilloma; Rats