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The high incidence of oesophageal cancer in Northern Iran has been associated with opium. N-Nitrosamines are the only carcinogens known to induce oesophageal cancer in animals. Ethanol, which is the major influence on oesophageal cancer incidence in the West, inhibits the first pass clearance of N-nitrosodimethylamine in animals and increases the alkylation of oesophageal DNA by oesophageal cancer-inducing N-nitrosamines. The experiments now reported were to test whether opium or morphine, which is the major alkaloid in opium, have a similar effect. It is shown that administration of morphine to rats does increase the ethylation of oesophageal DNA by N-nitrosodiethylamine and may reduce the first pass clearance of N-nitrosodimethylamine by the liver, but only at high doses of morphine.

The induction of sister chromatid exchange (SCE) by opium pipe scrapings (sukhteh, Su) and the pyrolysis products of opium (Op) and of its major alkaloids, morphine (Mo), have been compared with that of cigarette smoke condensate (CSC). All pyrolysates induced SCE and the frequency was further increased by the inclusion of S9-mix in the protocol. The pyrolysates of Op induced considerably more SCE than CSC when the same concentrations were compared on a weight basis, and the rank in order of potency in CHO cells was MO greater than Op greater than CSC greater than Su. The Op pyrolysates may therefore contribute a significant risk factor to the observed high incidence of oesophageal cancer in areas of Iran where heavy Op usage occurs.