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Is cadmium genotoxic?

T G Rossman¹, N K Roy, W C Lin

¹Institute of Environmental Medicine, New York University Medical Center, NY 10016.

IARC Scientific Publications

|January 1, 1992

Summary

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Cadmium(II) shows increasing evidence of mutagenicity, particularly in bacteria, potentially through indirect DNA damage and by inhibiting DNA repair mechanisms. This metal may also act synergistically with other mutagens and carcinogens.

Area of Science:

Environmental Toxicology
Molecular Biology
Genetics

Background:

Previous evidence for cadmium(II) mutagenicity in bacteria and mammalian cells was limited.
Recent protocol improvements have yielded stronger evidence for cadmium's mutagenic potential.
Potential confounding factors like cellular tolerance mechanisms require consideration.

Purpose of the Study:

To evaluate the mutagenic effects of cadmium(II) on biological systems.
To investigate the mechanisms underlying cadmium-induced DNA damage.
To explore the role of cadmium in DNA repair inhibition and synergistic effects with other agents.

Main Methods:

Assessment of mutagenicity in bacterial and mammalian cell systems.
In vitro studies exposing DNA to cadmium(II) and cadmium(II) hydrogen peroxide.

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Analysis of cellular responses including glutathione depletion and DNA repair inhibition.

Main Results:

Improved protocols demonstrate enhanced evidence of cadmium(II) mutagenicity, especially in bacteria.
Direct exposure of DNA in vitro did not cause strand breaks, suggesting indirect damage mechanisms.
Cadmium(II) induces a pro-oxidant state by depleting glutathione and inhibits DNA repair, acting as a clastogen.

Conclusions:

Cadmium(II) exhibits mutagenic and clastogenic properties, likely through indirect DNA damage and repair inhibition.
The cadmium-metallothionein complex may contribute to DNA strand breaks.
Cadmium(II) can potentiate the effects of other mutagens and carcinogens due to its DNA repair inhibitory action.