Inhibition by colchicine of changes in amino acid transport and initiation of DNA synthesis in regenerating rat liver.

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Abstract
The uptake of amino acids (measured with .alpha.-aminoisobutyric acid) by hepatocytes stimulated to proliferate by partial hepatectomy followed a biphasic pattern, with an initial peak 8-10 h after surgery followed by a release of amino acids between 10 and 16 h and a further increase between 16 and 20 h after the operation. The 2nd period of increased uptake coincided with the increase in DNA synthesis by the hepatocytes. Colchicine, and other microtubule disrupters administered at the time of partial hepatectomy, abolished the 1st period of increased amino acid uptake and prevented the cells from initiating DNA synthesis. Pulse-labeling experiments with .alpha.-aminoisobutyric acid revealed that colchicine did not inhibit amino acid transport per se, but prevented the increased capacity for amino acid transport induced by partial hepatectomy. An injection of colchicine 14 h after hepatectomy prevented the release of amino acids by the liver and also substantially reduced the initiation of DNA synthesis. The microtubules may play a role in proliferative activation and also in the initiation of DNA synthesis of hepatocytes in vivo and changes in amino acid transport seem to be linked to these microtubule-requiring processes.