<p>[Purpose] It is widely known that drug-induced gingival overgrowth is caused by the administration of an antihypertensive drug Amlodipine, the antiepileptic drug Phenytoin, or the immunosuppressant Cyclosporin A (CyA). The mechanism of gingival overgrowth is thought to be fibroblast overgrowth and collagen metabolism disorders due to the drug&apos;s direct action, but the details are unknown. Metallothionein (MT) is attracting attention as a multifunctional protein that has various roles such as detoxification of heavy metals as cadmium (Cd), and its relationship with proliferation has been suggested. In this study, we experimented to investigate the relationship between MT and drug-induced gingival overgrowth. [M &#x26; M] CyA or Cd was added to mouse gingival epithelial cells, and the changes in gene expression of MT or type I collagen (Col Ia) were analyzed 1, 3, 6 hours after CyA or Cd treatment by using real-time RT-PCR. In addition, the cytotoxicity was observed using lactate dehydrogenase assay, and cell viability assay. [Results] Cell viability and cytotoxicity in CyA treatment were not significant to control. The gene expression of MT increased after Cd or CyA treatment. The CyA treatment increased Col Ia gene expression after 1 hour. There is a difference in the reactivity of MT gene expression by the type of stimulation to gingival cells. [Conclusions] The MT of gingival cells could work as a multifunctional protein induced during proliferation as well as a biological defense reaction to heavy metal, it indicates the pharmacological significate of MT in gums.</p>