| 相互作用 | Tests were carried out in cultured Chinese hamster ovary (CHO) cells (line CHO-AA8-4) and in X-irradiated Syrian hamster embryo cells (SHE) to investigate the effects of butylated-hydroxyanisole (BHA) on the metabolism and mutagenic activity of benzo(a)pyrene (BaP) and to compare them with those induced by butylated-hydroxytoluene (BHT) and p-methoxyphenol (PMO). Feeder Syrian hamster embryo cells were cocultured with target Chinese hamster ovary cells to provide metabolic transformation of benzo(a)pyrene. The mutagenicity of benzo(a)pyrene in target Chinese hamster ovary cells was reduced by up to 60% by pretreatment with p-methoxyphenol, butylated-hydroxyanisole, or butylated-hydroxytoluene. In Syrian hamster ovary cells, the antioxidants tested inhibited metabolism with reduction in levels of water soluble benzo(a)pyrene glucuronide conjugates in the extracellular medium and apparent increase in levels of intracellular monophenols. As a result of the antioxidant inhibited formation of reactive, electrophilic benzo(a)pyrene metabolites, there was reduction in the binding of benzo(a)pyrene to nuclear macromolecules, especially to DNA.The modifying effects of para-methoxyphenol second stage treatment on N-methyl-N'-nitro-N-nitrosoguanidine initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt N-methyl-N'-nitro-N-nitrosoguanidine and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% para-methoxyphenol until week 52. para-methoxyphenol caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. Stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis.The modifying effects of five phenolic antioxidants on N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-initlated forestomach and glandular stomach carcinogenesis were investigated in male F344 rats. Groups of 20 rats were given an intragastric dose of 150 mg/kg body weight N-methyl-N-nitro-N-nitrosoguanine and starting from 1 week later received diet supplemented with 0.8% catechol, 1.0% 2-tert-butyl-4-methylphenol, 1.5% p-tert-butylphenol, 1.5% methylhydroquinone, 1.5% 4-methoxyphenol, or basal diet alone for 51 wk. Further groups of 10-15 rats were maintained as controls without prior treatment with N-methyl-N-nitro-N-nitrosoguanine. The incidences of squamous cell carcinoma of the forestomach in N-methyl-N-nitro-N-nitrosoguanine-treated animals were significantly elevated by the diets containlng catechol (P less than 0.001), 2-tert-butyl-4-methylphenol (P less than 0.001), or p-tert-butylphenol (P less than 0.01), while the development of carcinoma in situ was inhibited by 4-methoxyphenol (P less than 0.01). Treatment with catechol, 2-tert-butyl-4-methylphenol, p-tert-butylphenol, or 4-methoxyphenol alone induced forestomach hyperplasia at incidences of 86.7, 40, 93.3, and 100%, respectively. In the pyloric region of the glandular stomach, the development of adenomatous hyperplasia and adenocarcinoma after N-methyl-N-nitro-N-nitrosoguanine treatment was significantly enhanced by diet containing catechol (P less than 0.001). Moreover, treatment with catechol alone induced 100% adenomatous hyperplasia and induced adenocarcinoma in 20% of animals. ... While antioxidants causing proliferation in forestomach epithelium can markedly enhance carcinogenesis in this tissue, others displaying the same or greater potential for generating a hyperplastic response, like 4-methoxyphenol can exert an inhibitory effect. In addition, it was shown that catechol is an unequivocal glandular stomach carcinogen also possessing strong enhancing activity for N-methyl-N-nitro-N-nitrosoguanine-induced lesion development.The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000, 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in colon carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline) treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.For more Interactions (Complete) data for 4-METHOXYPHENOL (11 total), please visit the HSDB record page. |
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