Effect of the co-administration of phenobarbital, quercetin and mancozeb on nitrosomethylurea-induced pancreatic tumors in rats

• Published in: Food and chemical toxicology 2006-12, Vol.44 (12), p.2101-2105
• Main Authors: Valentich, M.A., Eynard, A.R., Barotto, N.N., Díaz, M.P., Bongiovanni, G.A.
• Format: Article
• Language: English
• Subjects: Alkylating Agents - toxicity; Animals; Animals, Newborn; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - pharmacology; Carcinoma in Situ - chemically induced; Carcinoma in Situ - pathology; Chemical agents; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Drug–drug interaction; Female; Fungicides, Industrial - toxicity; Gastroenterology. Liver. Pancreas. Abdomen; Hyperplasia - chemically induced; Hyperplasia - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Mancozeb; Maneb - toxicity; Maternal Exposure; Maternal-Fetal Exchange; Medical sciences; Methylnitrosourea - toxicity; Nitrosomethylurea; Pancreatic carcinogenesis model; Pancreatic Neoplasms - chemically induced; Pancreatic Neoplasms - pathology; Pesticides, fertilizers and other agrochemicals toxicology; Phenobarbital; Phenobarbital - pharmacology; Pregnancy; Quercetin; Quercetin - pharmacology; Rats; Rats, Wistar; Toxicology; Tumors; Zineb - toxicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2006.07.013

We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3–10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively. Conclusion: Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.