CADMIUM SELECTIVELY INHIBITS FIBROBLAST PROCOLLAGEN PRODUCTION AND PROLIFERATION

Chronic inhalation of cadmium fumes has been associated with the devel opment of emphysema, a disease characterized by extensive disruption o f lung connective tissue. Cadmium is also an important contaminant of tobacco and may play a role in cigarette smoking-related emphysema. In this paper we investigated the effect of nontoxic doses of cadmium ch loride (CdCl2) on fibroblast procollagen production and proliferation, key features of connective tissue repair following injury. CdCl2 inhi bited fibroblast procollagen production in a dose-dependent manner in two different cell lines. For fetal rat fibroblasts, maximal effects w ere observed at 10 mu M CdCl2, with values reduced by 82 +/- 6% (mean +/- SE, n = 6, P < 0.01) relative to control cells. In contrast, nonco llagen protein synthesis by these cells was enhanced in the presence o f CdCl2 In human fetal lung fibroblasts (HFL1), maximal inhibition of procollagen production (83 +/- 2%, P < 0.01) was observed at 40 mu M C dCl2, whereas noncollagen protein synthesis was unaffected. In both ce ll lines the inhibition of procollagen production was shown to be due to decreased procollagen synthesis and an increase in the proportion o f newly synthesized procollagen degraded. Cadmium also affected fibrob last proliferation in response to 2% serum, with values for fetal rat cells depressed by 17 +/- 4, 72 +/- 2, and 86 +/- 4% (all P < 0.01) co mpared with controls at 1, 5, and 10 mu M CdCl2, respectively. These d ata show that cadmium selectively inhibits fibroblast procollagen prod uction and also attenuates their mitogenic response to serum. These re sults are consistent with the hypothesis that cadmium may play a role in the pathogenesis of connective tissue abnormalities in the lungs of cigarette smokers and of humans exposed to cadmium fumes occupational ly.