Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protection from it by Brazilian propolis and artepillin C

In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA) in male ddY mice, primary pulmonary cancers were also induced in bronchiol ar and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxy guanosine (8-OHdG), products of oxidative processes, increased in bronchiol ar and alveolar cells after administration of Fe-NTA. These substances disa ppeared after oral administration of propolis or artepillin C, as shown his tochemically, and correlated with an anticancer prophylactic effect of prop olis and artepillin C. From our investigation, lipid peroxidation seems to play an important role in pulmonary carcinogenesis. Malignant progression f rom adenoma of bronchiolar or alveolar origin to malignant tumors has been proposed to involve a stepwise transformation. In our study, adenomas devel oped into adenocarcinomas and large cell carcinomas after treatment with Fe -NTA. In contrast, after oral administration of propolis or artepillin C, a denomas did not progress to carcinomas. Instead of developing into large ce ll cancers, as induced by Fe-NTA in control mice, adenomas showed remarkabl e proliferation of macrophages and local anti-oxidant activity after treatm ent with either propolis or artepillin C. Propolis and artepillin C therefo re appear to inhibit lipid peroxidation and the development of pulmonary ca ncers.