Is fumonisin B_(1) an aetiological agent in oesophageal cancer in South Africa?

N Singh, MMS , R Myburg, MMS , AA Chuturgoon PhD

Mycotoxin Research Unit, Nelson R Mandela School of Medicine, Faculty of Health Sciences, University of Natal, Congella, Durban, South Africa

AIM: To measure fumonisin B₁ (FB₁), sphinganine (Sa) and sphingosine (So) concentrations in sera of oesophageal cancer (OC) patients. In addition, lymphocyte apoptosis was determined in these OC patients. FB₁, was also immunolocalised in oc tissue and lymphocytes. METHODS Whole blood was centrifuged and the serum was removed and analysed for FB₁,Sa and So using reversed phase high pressure liquid chromatography (HPLC). Lymphocytes were isolated from OC patient bloods using density gradient centrifugation. The % apoptosis of the isolated lymphocytes was determined using Annexin V-FITC and propidium iodide (PI). The lymphocytes were then analysed on a FACSCalibur flow cytometer. OC tissue (biopsied) and isolated lymphoctes were processed scanning and electrom microscopy. Also, FB₁, was probed immunochemically using a monoclonal antibody. RESULTS OC serum FB₁ was shown to be present in in 80% of bloods analysed (113) with a mean concentration of 4.4ng/ml. Urine FB₁ concentration in these patients was 18.9ng/ml. The mean Sa and So OC serum concentration was 66 and 89ng/ml respectively. Control serum Sa and So concentrations were 35 and 105ng/ml respectively. A high percentage of OC patient lymphocyte apoptosis (44%) was observed as compared to control lymphocytes (4%). The presence of FB₁in OC tissue and lymphocytes was confirmed immunochemically. CONCLUSIONS OC patients contain high levels of FB₁ in serum. This FB₁ is known to disrupt sphingolipid metabolism as evidenced by the altered ratio of Sa and So. In addition FB₁is known to induce apoptosis, which is shown by the high levels in the lymphocytes of OC patients. FB₁ was actively metabolised in these OC patients and is seen abundantly in biopsied tissue and lymphocytes.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 996 (Genetic & environmental interactions).