The Effects of Drugs, Other Foreign Compounds, and Cigarette Smoke on the Synthesis of Protein by Lung Slices

Abstract

The incorporation of "4C-leucine into rabbit lung slices was monitored in the absence and presence of selected drugs and chemicals relevant to the perturbation of lung function and the development of lung disease. Known inhibitors of protein synthesis (cycloheximide and ricin) inhibited the incorporation of "4C-leucine. Marked inhibition was also recorded with the lung toxins paraquat and 4-ipomeanol.By contrast, orciprenaline, salbutamol, and terbutaline were without effect although some response was recorded with isoprenaline. The filtered gas phase of cigarette smoke and acrolein, one of its components, were inhibitory but protection was afforded by N-acetylcysteine. It is suggested that the inhibitory effects of cigarette smoke may be due to its acrolein content. It is further suggested that the use oflung slices and measurements of 14C-leucine incorporation provide valuable means for monitoring potential pulmonary toxins.

Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression

“…Cigarette smoke-induced inhibition of global protein synthesis has been demonstrated by several groups in different tissues/cell types (lung, alveolar macrophages, and liver), and in both in vitro and in vivo animal models (Yeager, 1969;Garrett and Jackson, 1979;Hamosh et al, 1979;Leffingwell and Low, 1979;Hellstern et al, 1990). The mechanism of CSC-induced protein synthesis inhibition remains enigmatic.…”