Abrogation of cyclin D1 expression predisposes lung cancer cells to serum deprivation-induced apoptosis

Cyclin D1 antisense (D1AS)-transfected lung epithelial cell lines were seru m deprived and then analyzed for three hallmarks of apoptosis: appearance o f single-strand DNA breaks, alteration of apoptosis-related protein express ion, and induction of chromatin condensation. Single-strand DNA breaks appe ared at significant levels 24 h after serum deprivation, whereas induction of chromatin condensation was observed after 72 h. The antioxidants dimethy l sulfoxide, ascorbate, and glutathione, as well as insulin-like growth fac tor-I, inhibited induction of DNA damage in this assay. Additionally, proli ferating cell nuclear antigen expression is completely suppressed in the D1 AS cells, indicating a mechanism to explain the reduced capacity for DNA re pair. Increased expression of cyclin DI, which is a common lesion in lung c ancel; may thus prevent induction of apoptosis in an oxidizing and growth f actor-poor environment. Reducing cyclin D1 expression in lung cancer cells by expression of D1AS RNA disrupted these protective pathways.