Background and Aim: To determin the most sensitive tissues to carcinogenic effect of urethane and co-carcinogenic effect of sodium nitrite by investigation of histopathological variations in different tissues of balb/c mice.

Materials and Methods: An experimental study in 40 inbred balb/c mice aged 9-11 weeks was designed. The samples were classified into 4 groups: The first group was mice treated with 50 mg/l sodium nitrite in 0.9% NaCl instead drinking water SN&NaCl). The urethane group (U) was characterized by intraperitoneal injection of 3 times urethane (600 mg/ kg/day at 48 hour intervals). The third group was given 50 mg/l sodum nitrite in drinking water (U&SN) following the same intake of urethane as the second group, and the forth one was the control group. All mice were sacrificed after 20 weeks; tissues were removed and examined for histopathological changes. Data analyzed by Fisher exact test.

Results: The formation of lung tumor was, significantly, increased in the urethane group as compared with the control group & (NS+Nacl) groups ( respectively P<.004 & P<.02) and in (U+NS) group as compared with the control group & (NS+Nacl) groups ( respectively P<.003 & P<.02). In females mice also The formation of lung tumor was, significantly, increased in the urethane group as compared with the control group & (NS+NaCl) groups (P<.05) and in the (U+NS) group was significantly higher than those in (C) & (NS+NaCl) groups (P<.009). The formation of lung adenocarcinomas was, significantly, increased in the (U+NS) group as compaired with the (C) & (NS+Nacl) groups (P<.003). In females mice also the formation of lung adenocarcinomas was, significantly, increased in the (U+NS) group as compaired with the (C) & (NS+Nacl) groups (P<.009) and (U) group (p<.05).The frequencies of stomach and testis hyperplasia and metaplasia in different groups did not show any significant differences. There was no histopathological variation in other tissues.

Conclusion: Our results showed the tumorigenic effect of urethane in lung tissue. Sodium nitrite increases tumorogenic effect of urethan. Sodium nitrite increases carcinogenic effect of urethan (This result is the first study that suggest sodium nitrite increases carcinogenic effect of urethan).Urethan increases co-carcinogenic effect of sodium nitrite.