The first study to test for DNA adducts as a marker for intrahepatic cancer of the bile duct has lent more support to the hypothesis that toxins damaging DNA lead to cancer. Greater exposure to environmental toxins may explain the rapid rise in deaths from this cancer in Western countries over the past 30 years, suggest the authors.
Patients with the cancer had more DNA adducts in samples of their tumour or adjacent to their tumour than patients without (median relative amounts/108 nucleotides: tumour DNA 7.2 (range 1.8–48.4); tumour adjacent DNA 8.6 (1.2–51.6) v non-cancer DNA 2.9 (0.6–11.5)). The pattern and density of DNA adducts differed between tumour DNA and tumour adjacent DNA and between each of these and non-cancer DNA.
Tumour tissue was taken from 32 men with primary intrahepatic cholangiocarcinoma and tumour adjacent tissue from 28 of them. Cystic ducts were obtained from seven cancer free patients during surgery for gall stones. Adducts were detected in DNA extracted from each sample by 32P postlabelling assays, TLC separation, and autoradiography. Positive and negative controls were included.
DNA adducts are modified DNA bases formed when electrophilic carcinogens or their metabolites bind to DNA. They are key to chemically induced mutagenesis through misrepair or absence of repair and are markers for chemical mutagenesis, but not hitherto in bile duct tissue, even though the liver and biliary system metabolise carcinogens. Intrahepatic bile duct cancer is the second commonest liver cancer worldwide, but the cause of its prominence is unknown.
▴ Gut 2003;52:586–591.