Guinea-pig α1-fetoprotein: purification, characterization, developmental and hormonal regulation, and behavior in diethylnitrosamine hepatocarcinogenesis

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Abstract
Physicochemical and immunological procedures were developed for the purification of guinea pig .alpha.1-fetoprotein (AFP). A double-antibody radioimmunoassay was developed which can detect 0.1 ng of AFP. The .**GRAPHIC**. of guinea pig AFP is 6.6. Its MW is 73,000. Its amino acid composition is similar to other AFP, but it has a higher carbohydrate content (8.5%), owing the larger amounts of mannose and N-acetylglucosamine. Guinea pig AFP has a slower electrophoretic mobility than other AFP, owing to its more basic ionic structure. It separates into 3 electrophoretic variants in nondenaturing polyacrylamide gels; these are charge variants with isoelectric points of 5.0, 5.12 and 5.54. Changes in electrophoretic mobility after neuraminidase treatment indicate that charge heterogeneity is due to a variable content in sialic acid. Guinea-pig AFP has fatty-acid- and lectin-binding properties, but no affinity for sex hormones. Its biological half-life is 2.1 days. Its sites of synthesis are the liver and the yolk sac, with minor contributions by the upper gastrointestinal tract. AFP production appears to cease synchronously in the liver and yolk sac during the 8th week of gestation. From 4-8 wk of gestation, AFP levels are at 2.5-3.5 mg/ml in fetal serum and 0.1-0.2 mg/ml in amniotic fluid. The proportion of electrophoretic and lectin-reactive AFP variants changes during development, reflecting the changing glycosylation of the protein. The gestational levels of AFP in the maternal compartment are indicative of a fetomaternal equilibration through transamniotic exchange. Serum AFP levels in normal adult guinea pigs are remarkably high, from 400 to 2000 ng/ml and occasionally up to over 5000 ng/ml. The administration of dexamethasone suppresses serum AFP levels. During liver carcinogenesis induced by diethylnitrosamine, serum AFP levels increase, moderately, when tumors develop.