Tumor induction by concurrent oral administration of ethylenethiourea and sodium nitrite in mice

Carcinogenic potential of ethylenethiourea (ETU) in combination with sodium nitrite was investigated in ICR mice of both sexes. Groups of 30 males and 30 females each were given 10 weekly oral administrations of ETU and sodium nitrite with the following combinations of dosing (ETU vs sodium nitrite, mg/kg/wk): 0 vs 0, 100 vs 0, 0 vs 70, 25 vs 17.5, 50 vs 35, and 100 vs 70. Thereafter, the animals were allowed to live without treatment up to 18 mo after the first administration. Concurrent administration of ETU and sodium nitrite caused earlier development of tumors and/or dose-dependent increases in the incidences of tumors in the lymphatic tissue, lung, forestomach, Harderian gland, and uterus, whereas treatment with either ETU or sodium nitrite failed to show carcinogenic activity. In addition, carcinomas in the forestomach and uterine horn were limited to mice receiving concurrent administrations of ETU and sodium nitrite. These results indicate that ETU is most probably converted in vivo into N-nitroso ETU and that the N-nitroso ETU has a greater carcinogenic potential in mice than ETU alone.