Comparison of the subacute effects of cadmium exposure upon nucleic acid, cyclic adenosine 3′, 5′-monophosphate and polyamine metabolism in lung and kidney cortex

Document Type



Brain and Mind Institute


The timecourse of the cadmium-inflicted changes in DNA, polyamines, and cyclic AMP has been investigated in lung and renal cortex tissue of rats. In pulmonary tissue, heavy metal administration (2 × 1.0 mg/kg/day) produced an initial depression in the incorporation of [14C]-thymidine into DNA after 3 days, followed by a subsequent, significant enhancement at 5 days with maximal augmentation occurring after 7 days of cadmium treatment. In contrast the incorporation of labeled thymidine into kidney cortex DNA was decreased at all time periods studied and statistically significant reduction to at least half of the control values was noted at 3, 5 and 7 days. No apparent differences were found between pulmonary and renal DNA concentrations which were decreased at 1 day and elevated after 7 days of cadmium exposure in both tissues. Whereas cadmium significantly lowered lung RNA concentrations after 1, 3, or 5 days, heavy metal treatment failed to produce any significant change in RNA content of the kidney cortex. In general, subacute exposure to cadmium resulted in a significant rise in pulmonary putrescine, spermidine, and spermine after 3 and 5 days, although a significant depression was observed at 7 days in the case of putrescine. Surprisingly, the renal concentrations of putrescine and spermine were elevated in metal-treated animals but there was a statistically significant reduction in spermidine content. As in the case of incorporation of [14C]-thymidine into DNA, pulmonary cyclic AMP concentrations were depressed initially at 1 day and continuation of cadmium treatment for 3, 5, or 7 days resulted in enhancement of cyclic nucleotide concentration. In contrast, administration of the heavy metal lowered both the incorporation of thymidine into DNA and the concentration of cyclic AMP in renal cortex at all time points examined. The data demonstrate that even though the responsiveness of lung to subacute cadmium exposure differs from that of kidney cortex, the observed alterations in DNA synthesis may be mediated through modulation of cyclic AMP (and possibly polyamine levels) in both tissues.


This work was published before the author joined Aga Khan University.


Toxicology and Applied Pharmacology