Evidence for stimulatory and inhibitory effects of cadmium on the [3H]thymidine incorporation into various organs of the mouse

Toxicology. 1986 Jul;40(1):13-23. doi: 10.1016/0300-483x(86)90042-9.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium
  • DNA / biosynthesis*
  • Dose-Response Relationship, Drug
  • Male
  • Methylcholanthrene
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • Thymidine / metabolism

Substances

  • Cadmium
  • Methylcholanthrene
  • DNA
  • Thymidine