[en] The environmental or silent smoke of tobacco contains a large number of components, and many of them are toxic to the epithelial cells. The environmental smoke contains reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are responsible for 50% of the global mortality, and also 56% of the disease burdens are attributed to tobacco in developing countries. The aim of the present study is to evaluate the effects of ROS and RNS on antioxidant enzymes and expression of eNOS and iNOS genes that synthesis NO in addition to the gene expression of MUC5AC that synthesis mucin. Moreover, the present study aimed also to evaluate the role of N-acetylcysteine (NAC) as antioxidant. Male guinea pigs exposed to cigarette smoke and/or gamma radiation were treated with N-acetylcysteine (NAC). The study included determination of the activities of Cu-Zn superoxide dismutase, Mn-superoxide dismutase, glutathione peroxidase in lung and heart and expressions of eNOS, iNOS and MUC5AC genes in lung tissue. The results revealed significant increase in Mn-superoxide dismutase, iNOS gene expression and MUC5AC gene expression, and significant decrease in eNOS gene expression in lung of guinea pig exposed to cigarette smoke and/or gamma radiation. The results also revealed that NAC can reduce the effects of cigarette smoke and radiation on antioxidant enzymes and the expression of genes that synthesis NO and MUC5AC that synthesis mucin. It could be concluded that NAC can ameliorate the action of the bad effects of cigarette smoke and gamma radiation.