Xenobiotics and tropical chronic pancreatitis

The prevalence of chronic pancreatitis in tropical zones is far higher than in temperate zones, but there is no explanation for this difference. Detailed social, occupational, and dietary histories were taken from 79 patients attending two hospitals in Madras, South India. There were 53 apparently sporadic cases with both pancreatic calculi and diabetes; six apparently sporadic cases with noncalcific disease, usually with diabetes; four pairs of first-degree relatives with either calcific or noncalcific disease, with or without diabetes; and two families in which several members had one or another variant of the disease. Three trends emerged from these histories: 1. Regular exposure to a xenobiotic inducer of cytochromes P450I (smoke from cigarets, burning firewood, or vehicle emissions; a cooking oil composed of C18:2 fatty acids); 2. Concurrent exposure to a chemical that undergoes metabolic activation (petroleum products, notably kerosene fumes; cyanogenic glycosides; solvents; paint); and 3. Low intakes of micronutrients required to synthesize/refurbish glutathione. These trends, similar to those noted at Manchester, North West England, suggest a unifying template for tissue damage in chronic pancreatitis, namely, heightened but unmitigated oxidative detoxification reactions mediated by cytochromes P450. The higher prevalence of the disease in underprivileged communities of the tropics may reflect poorer dietary availability of micronutrient antioxidants.