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Experimental study reveals impaired asialoglycoprotein uptake and attachment in pre-nodular rat hepatocytes, indicating early receptor loss during chemical carcinogenesis.
Endocytosis and degradation of asialo-glycoprotein were investigated in hepatocytes from carcinogen-treated rats. The cells were isolated at an early stage of carcinogenesis after a sequential treatment with diethylnitrosamine and 2-acetylaminofluorene. Hepatocytes at this pre-nodular stage take up asialo-orosomucoid at a lower rate than hepatocytes from normal rats, whereas degradation of the protein occurs at a similar rate in the two populations. The lower rate of uptake appears to result from a decreased binding capacity in treated hepatocytes. The reduced binding capacity leads to slower kinetics of cell attachment to a substratum of asialo-glycoprotein. The lower number of receptors did not seem to be confined to a particular subpopulation of hepatocytes. Diploid and tetraploid hepatocytes, isolated by centrifugal elutriation, displayed the same reduction in binding capacity.
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Schwarze et al. (1987) studied this question.
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