DNA repair synthesis in primary culture of bovine bile duct epithelial cells induced by chemical agents in relation to bile duct cancer

Abstract

Unscheduled DNA synthesis (UDS) was measured autoradiographically in a primary culture of extrahepatic bile duct epithelial cells of Holstein cows following exposure to chemicals known to be capable of developing bile duct cancers in experimental animals, i.e., N-methyl-N′-nitro-N-nitrosoguanidine (MNNG, CAS No. 70-25-7), N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG, CAS No. 4255-77-6), 20-methylcholanthrene (MCA, CAS No. 56-49-5), N-nitrosodimethylamine (DMN, CAS No. 62-75-9) and aflatoxin B₁ (AFB₁, CAS No. 1162-65-8). MNNG and ENNG induced UDS without addition of S9 mixture. MCA elicited UDS only if S9 mixture was added. Regardless of the presence or absence of S9 mixture, DMN failed to induce UDS. DNA repair by AFB₁ was enhanced by the presence of S9 mixture. Therefore, for MNNG, ENNG and high doses of AFB₁ activation by the liver is not necessary to exert genotoxic effects and they seem to be capable of direct action on bile duct epithelial cells in the presence of a bilioenteric fistula or anastomosis.