Molecular mechanisms of control of albumin and alphafetoprotein production: a system to study the early effects of chemical hepatocarcinogens.

The cellular mechanism of control of alphafetoprotein (AFP) and albumin (ALB) production during normal and pathologic permissive states is being examined using complementary DNA probes. AFP is the major serum protein for most of fetal life, but normally is produced in very small amounts in the adult. AFP production recurs in the adult during restitutive proliferation of the liver following partial hepatectomy or chemical injury, early after the exposure to chemical carcinogens and in animals with hepatocellular or yolk sac carcinomas. AFP production is roughly proportional in each case examined so far to the amount of mRNA available. On the other hand, there appears to be no difference in the gene number or gene organization in permissive or non-permissive states and there is no evidence of selective degradation of AFP or AFP (and ALB) production is probably at the level of gene transcription. Understanding of how carcinogens act to permit expression of the AFP gene may lead to important insights into carcinogenic mechanisms.