Agent Orange and the Vietnamese: the persistence of elevated dioxin levels in human tissues.

OBJECTIVES: The largest known dioxin contamination occurred between 1962 and 1970, when 12 million gallons of Agent Orange, a defoliant mixture contaminated with a form of the most toxic dioxin, were sprayed over southern and central Vietnam. Studies were performed to determine if elevated dioxin levels persist in Vietnamese living in the south of Vietnam. METHODS: With gas chromatography and mass spectroscopy, human milk, adipose tissue, and blood from Vietnamese living in sprayed and unsprayed areas were analyzed, some individually and some pooled, for dioxins and the closely related dibenzofurans. RESULTS: One hundred sixty dioxin analyses of tissue from 3243 persons were performed. Elevated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) levels as high as 1832 ppt were found in milk lipid collected from southern Vietnam in 1970, and levels up to 103 ppt were found in adipose tissue in the 1980s. Pooled blood collected from southern Vietnam in 1991/92 also showed elevated TCDD up to 33 ppt, whereas tissue from northern Vietnam (where Agent Orange was not used) revealed TCDD levels at or below 2.9 ppt. CONCLUSIONS: Although most Agent Orange studies have focused on American veterans, many Vietnamese had greater exposure. Because health consequences of dioxin contamination are more likely to be found in Vietnamese living in Vietnam than in any other populations, Vietnam provides a unique setting for dioxin studies.

Enhancing effect of alpha-interferon on the C2 synthesis by cultured human monocytes.

C2 synthesis by human peripheral blood monocytes cultured in the presence of human alpha-interferon (IFN-alpha) was studied. IFN-alpha was added in different amounts (1-1000 IU/ml) to the cultures on day 3 and was removed on day 7. As control, mock interferon (m-IFN) was also tested. C2 content of the culture supernatants was measured by immunohaemolytic method. IFN-alpha was found to enhance C2 synthesis in a dose-dependent way. The enhancing effect could be observed even after the removal of IFN-alpha. C2 production by the cultured monocytes was increased by m-IFN as well; the extent of enhancement however, was found to be significantly lower than that induced by the corresponding amount of IFN-alpha. In contrast to the enhancing effect on C2 production, IFN-alpha did not influence total protein synthesis in the cultures, suggesting a selective stimulatory action on the C2 gene.

Serial complement measurements in patients with leukaemia.

Haemolytic activity of the classical and alternative pathways and the levels of C4, C3 and factor B were serially measured in 153 serum samples of 41 patients with different types of leukaemia (9 AML, 14 ALL, 10 CML and 8 CLL). In parallel, the concentration of circulating immune complexes (CIC) was estimated using two methods, the complement consumption assay and the Clq-solubility test. Different complement profiles were found in different types of leukaemia. In AML, each complement parameter tested was elevated as compared to the control values (sera of healthy blood donors). Similar results were observed in ALL, although the differences were less marked. In CML, dissociation of the classical and alternative pathway activities was found: activities of the classical pathway and C4 were significantly elevated, whereas activity of the alternative pathway as well as C3 and factor B concentration did not differ significantly from the control values. In CLL, normal or slightly depressed complement levels were found. The concentration of circulating immune complexes measured by both methods was significantly increased as compared to control values. No significant positive or negative correlations were found between the complement levels and the immune complex concentrations determined in the same sera. An association between the clinical course of acute leukaemia and the complement levels was observed: significantly elevated complement titres were found in the blastic stage of the disease, whereas in remission normal values were recorded. The results of complement measurements performed in serum samples obtained before and after combination chemotherapy were compared on 32 occasions. In parallel to a significant decrease in the absolute number of blast cells in the peripheral blood, a normalization of the increased complement levels was observed after treatment.