Conjugation pathways in human bronchial carcinoma cell lines

Abstract

Human bronchial carcinoma cell lines in monolayer cell culture were used to study the conjugation of 1-naphthol and 3-hydroxybenzo( a)pyrene, two phenolic substrates. Cell lines, able to metabolise 1-naphthol to glucuronic acid and sulphate ester conjugate, showed a predominance of glucuronidation. This is in sharp contrast to normal human peripheral lung which metabolises these phenolic substrates predominantly to the sulphate ester conjugates. The bronchial tumour cell lines do not all have the same conjugation pattern and they differ in the metabolism of phenolic substrates when compared to normal peripheral lung. The cell lines generally show that sulphate enter conjugation was either reduced or absent. In some cases, dependent on the type of tumour the cell line was derived from, glucuronic acid conjugation was elevated. Initial sub-cellular studies with a poorly differentiated epidermoid cell line (Ben) demonstrated that this line had an active UDP-glucuronosyltransferase ( K m 33 μM and V max 1.8 nmoles min −1 mg protein −1), using 1-naphthol as substrate. However, this cell line was unable to form significant amounts of sulphate ester conjugates, due to either low sulphotransferase activity, or an inability to generate adenosine 3′-phosphate 5′-sulphatophosphate (PAPS).