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


CONCLUSIONS
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.
Valentich
M A
MA
2(a) Cátedra de Biología Celular, Histología y Embriología, Instituto de Biología Celular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina. mvalent@cmefcm.uncor.edu
Eynard
A R
AR
Barotto
N N
NN
Díaz
M P
MP
Bongiovanni
G A
GA
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D002273:Carcinogens / Q000494:pharmacology*; D002278:Carcinoma in Situ / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D008344:Maneb / Q000633:toxicity*; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008770:Methylnitrosourea / Q000633:toxicity; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015038:Zineb / Q000633:toxicity*
D000477:Alkylating Agents; D002273:Carcinogens; D005659:Fungicides, Industrial; D008344:Maneb; D008770:Methylnitrosourea; D011794:Quercetin; C013099:mancozeb; D015038:Zineb; D010634:Phenobarbital