Presence of albumin-positive cells in the liver of analbuminemic rats and their increase on treatment with hepatocarcinogens

Abstract

The analbuminemic rat is a mutant in which albumin mRNA processing is blocked owing to a seven-base-pair deletion in the 9th intron of the albumin gene. A small amount of albumin is detected in the serum of this rat. Production of serum albumin in the liver of this mutant rat was studied by an immunohistochemical method. The results showed that a few albumin-positive cells were present in the liver of the mutant rat, whereas all the hepatocytes in normal rat liver were albumin-positive. In the mutant the number of albumin-positive cells increased with age: their frequency was 10(-5) at birth and 6 X 10(-3) at 45 weeks of age. On administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 2-acetylaminofluorene, albumin-positive cells increased dramatically. Their numbers were 7 to 10 times those of untreated rats after 10 to 16 weeks of carcinogen treatment. The number of albumin-positive cells did not decrease after 3'-Me-DAB feeding was discontinued. In regenerating liver after partial hepatectomy, clusters of albumin-positive cells increased while the number of singlet albumin-positive cells decreased. These observations suggest that the appearance of albumin-positive cells in analbuminemic rat liver may be due to a somatic mutation of the hepatocytes.