-Background -The high incidence of esophageal cancer in the north of Iran has been associated to the consumption of opium and exposure to nitrosamines. Diethylnitrosamine has an established potential of producing experimental cancer in the esophagus and liver. Aim -To evaluate by histopathology the effect of oral administration of morphine and diethylnitrosamine during 23 weeks on the hepatic and esophageal carcinogenesis on 176 rats. Esophageal cancer is among the 10 most frequent in the world and if we consider the social impact on the endemic regions, the problem becomes a severe scourge for those populations. An intimate correlation has been seen between sickness and regional habits, meaning the way people live (43) , and it has been shown that the origin of esophageal cancer is associated with different factors in each region (16,26) . The high incidence of esophageal cancer has been associated with the consumption of opium habit in high-incidence regions in the north of Iran (15,19,24) and with the exposure to nitrosamines in China, mainly through their diet (8,21,22,41) . The reasons for the association between opium and cancer of the esophagus are not known, but trials show that a dose of morphine sulfate, the main alkaloid of opium, caused an alkylation increase in the DNA in the esophagus and a decrease in the liver in rats that received diethylnitrosamine (DEN) after the morphine. DEN, a nitrosamine, is considered one of the substances with the highest potential for producing cancer in the esophagus and liver of rats and mice (20,31) , and the alkylation of the DNA constitutes a known alteration precursory to the carcinogenesis provoked by DEN in these organs. This way the morphine would cause a lowering of the hepatic carcinogenesis and an increase of the esophageal by influencing the hepatic metabolism of DEN. Once suggested that the observations made in rats could be imputed to man (31) , these would be possible metabolic evidences, in an acute trial, for the association between opium and cancer of the esophagus in rats and therefore, by extension, in humans.In the present study, we offered DEN in the rat's drinking water for 3 days during each one of the 23 weeks, and compared with the groups that consumed morphine simultaneously or not with DEN. We evaluated the effect of the chronic administration of morphine and DEN on the hepatic and esophageal carcinogenesis.We purchased the DEN from SIGMA (St. Louis, MO, USA): N-0756, density -0.95 g/mL, and the morphine sulfate from CRISTÁLIA (Itapira, SP, Brazil): DCB 0856.03-7, density -10 mg/mL. We obtained the 176 Wistar rats, ranging from 185-215 g, from Bioterio of the State Foundation of Health Protection and Research in Rio Grande do Sul,
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