Evidence for stimulatory and inhibitory effects of cadmium on the [3H]thymidine incorporation into various organs of the mouse.
The effects of cadmium chloride on the DNA turnover in various organs of the mouse were evaluated by measuring the incorporation of intraperitoneally injected [6-3H]thymidine. This approach is considered to be a useful complement to other short-term in vivo tests in the screening for genotoxic properties of chemicals. A moderate amount of CdCl2 (1 mg/kg body wt) lacked inhibitory effects on the incorporation of [3H] thymidine, but produced a significantly increased uptake of the DNA precursor into the liver. Whereas the genotoxic polycyclic aromatic hydrocarbon 3-methylcholanthrene suppressed the [3H]thymidine incorporation into several organs when given in a dose of 30 mg/kg body wt, cadmium chloride was inhibitory only when injected in a sublethal dose (4 mg/kg body wt). When the injected amount of CdCl2 was 4 mg/kg, an initial and transient inhibition of the [3H]thymidine incorporation was observed in several organs. After extending the time between the injection of cadmium and sacrifice to 72 h, such a high dose of cadmium produced potent stimulatory effects on the [3H]thymidine incorporation not only into the liver but also into the pancreas, kidney, small intestine, and testis. The mechanism behind the cadmium-induced stimulation of the DNA synthesis remains obscure but may be due to an increased biosynthesis of the cytoplasmatic protein metallothionein. The stimulatory effects of cadmium on the incorporation of [3H]thymidine correlate well both with reported sites of extensive accumulation of the heavy metal and the presence of high concentrations of cadmium-induced metallothionein.
D000818:Animals; D002104:Cadmium; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D013936:Thymidine / Q000378:metabolism
D002104:Cadmium; D008748:Methylcholanthrene; D004247:DNA; D013936:Thymidine