INHIBITION OF ALPHA-FETOPROTEIN PRODUCTION IN A HEPATOMA-CELL LINE BYANTISENSE OLIGONUCLEOTIDE ANALOGS

alpha-Fetoprotein (AFP) is a fetal protein which is absent in adult se rum, However, the AFP gene is expressed in some neoplastic cells, Acco rding to the literature, AFP may play a role in accelerating the growt h of cancer cells, In this report, 15 meric antisense oligonucleotide analogues (phosphorothioates and methylphosphonates) and their chimeri c forms, which were complementary to different regions of AFP mRNA, we re synthesized, and their physical characteristics such as stability, melting temperature, and toxicity were compared, They were examined as to their inhibitory effects on the translation of AFP mRNA in a AFP-p roducing hepatoma cell line, HuH-7. We found that chimeric oligomers w ith methylphosphonate or phosphorothioate linkages at both the 5' and 3' ends were more effective than prototypic oligomers, Inhibition of 7 2% was achieved with a chimeric oligomer against the translational ini tiation region, at a concentration of 25 mu M. No suppressive effect o f the oligomers was observed on cell viability or albumin production, indicating the specificity of the inhibition.