The transition metal cadmium is a pervasive and persistent environmental contaminant that has been shown to be both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes encoding stress-response proteins. In most cases, the mechanism by which cadmium affects the expression of these genes remains unknown. We have identified multiple novel cadmium-responsive genes in C. elegans using differential display technique. One of the genes, designated
cdr-1 , was selected for further analysis. The
cdr-1 cDNA encodes a 32 kDa, integral membrane protein that is identical to the C. elegans F35E8.11 predicted gene product. The rate of
cdr-1 mRNA accumulation following cadmium exposure is significantly greater than either of the C. elegans metallothioneins. This suggests that CDR-1 may function in the defense against cadmium-induced toxicity. Several putative upstream regulatory elements (URE) are identified in the
cdr-1 promoter. Potential UREs include a metal-responsive element, a heat-shock element, cAMP-response element, and AP-1 and GATA elements. Transgenic C. elegans carrying
cdr-1/lacZ reporter transgene and whole-mount in situ hybridization were used to determine the cell-specific pattern of
cdr-1 gene expression. When nematodes were treated with cadmium,
cdr-1 is exclusively transcribed in intestinal cells throughout post-embryonic stages of developmental. In the absence of cadmium,
cdr-1 gene expression is not observed at any developmental stage. Together, these results suggest that
cdr-1 is regulated in a cadmium-inducible and cell-specific fashion. The effects of other stressors including transition metals (e.g., zinc, copper, mercury, lead), oxidative stress, and heat shock on
cdr-1 transcription was evaluated using transgenic C. elegans . Exposure of transgenic C. elegans to various stressors failed to induce reporter transgene expression. These results suggest that
cdr-1 specifically responds to cadmium, indicating that
cdr-1 transgene can serve as a sensitive biomonitor of cadmium contaminant.