Guanylyl cyclase C (GCC) has been detected only in intestinal mucosa and colon carcinoma cells of placental mammals. However, this receptor has been identified in several tissues in marsupials, and its expression has been suggested in tissues other than intestine in placental mammals. Selective expression of GCC by colorectal tumor cells in extraintestinal tissues would permit this receptor to be employed as a selective marker for metastatic disease. Thus, expression of GCC was examined in human tissues and tumors, correlating receptor function with detection by PCR. GCC was detected by ligand binding and catalytic activation in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues or tumors. Similarly, PCR yielded GCC-specific amplification products with specimens from normal intestine and primary and metastatic colorectal tumors, but not from extraintestinal tissues or tumors. Northern blot analysis employing GCC-specific probes revealed an Ϸ4-kb transcript, corresponding to recombinant GCC, in normal intestine and primary and metastatic colorectal tumors, but not in extraintestinal tissues. Thus, GCC is selectively expressed in intestine and colorectal tumors in humans and appears to be a relatively specific marker for metastatic cancer cells in normal tissues. Indeed, PCR of GCC detected tumor cells in blood from some patients with Dukes B colorectal cancer and all patients examined with Dukes C and D colorectal cancer, but not in that from normal subjects or patients with Dukes A colon carcinoma or other nonmalignant intestinal pathologies.

Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.

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Drug‐induced gingival overgrowth is an adverse side effect associated principally with 3 different types of drugs; specifically the antiepileptic phenytoin, the calcium channel antagonist nifedipine, and the immunosuppressant cyclosporin. The present study has analyzed the effect of cyclosporin and lipopolysaccharide on fibroblasts from 3 different sources: 1) normal healthy human gingiva (NHGF); 2) overgrown gingiva from 2 patients taking cyclosporin (CHGF); and 3) human fetal lung (WI‐38). Fibroblasts isolated from cyclosporin‐associated gingival overgrowth were significantly less responsive to cyclosporin in terms of DNA, total protein, and proteoglycan synthesis. This finding supports the in vivo response where few fibroblasts are seen but marked overgrowth of fibrous tissue occurs. Lipopolysaccharide derived from Fusobacterium nucleatum and Escherichia coli was capable of inhibiting DNA synthesis significantly in all 3 fibroblast types. Total protein synthesis by CHGF cells was inhibited differentially by Fusobacterium nucleatum LPS and addition of cyclosporin to this system resulted in reversal of the inhibition. A synergistic effect was noted when the proteoglycan output of NHGF cells was assessed in response to co‐incubation with cyclosporin and Escherichia coli LPS. The study shows that bacterial LPS may be an important co‐factor in the pathogenesis of cyclosporin‐induced gingival overgrowth. J Periodontol 1992; 63:397– 404.

Pharmacogenic pigmentation of the oral mucosa has been reported following the use of a number of anti‐malarial drugs. The nature and distribution of the pigment is inconclusive in the literature. The aim of the present study was to document pigment deposition within the oral mucosa of DA rats following prolonged chloroquine and pyrimethamine administration. The drugs were given as a combined dosage and separately to different groups via stomach gavage tube. After 12 weekly administrations the palatal mucosa was examined histochemically and ultrastructurally for changes in numbers and size of active melanocytes using the dopa‐oxidase technique. The serum was analysed for changes in ACTH and testosterone levels. Morphometric analysis of cells incubated for dopaoxidase showed a significant increase in the size of dopa positive cells with both drugs but an increase in the number of active melanocytes with chloroquine only. Serum levels of ACTH remained unchanged with both drugs but pyrimethaminc caused an elevation in testosterone.