Albumin-negative hepatocytes in Sprague-Dawley x analbuminemic F1 rats treated with hepatic carcinogens.

Analbuminemic rats (NAR) are a mutant breed with an inherent inability to synthesize albumin. However, heterozygous rats born of a pair of NAR and Sprague-Dawley (SD) rats can synthesize albumin. Immunohistochemical staining for albumin shows that, although the majority of hepatocytes of SD x NAR F1 (female SD x male NAR) rats are positive for albumin, a small number of hepatocytes are negative. These albumin-negative hepatocytes are frequently found in the form of clusters which appear cytologically normal. When the rats were given a dietary regimen of 2-acetyl-aminofluorene (2-AAF), there was a significant increase in the number of albumin-negative hepatocytes. On the other hand, diethylnitrosamine (DEN) or 5-azacytidine did not increase the number of albumin-negative hepatocytes. 2-AAF and DEN also induced enzyme-altered hepatocytes but the albumin-negative hepatocytes were of a completely different class from the enzyme-altered hepatocytes. The results of this study indicate that some kind(s) of carcinogens induce mutated hepatocytes which are probably not involved in carcinogenesis.