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Effect of Size on Portal Circulation of Hepatic Nodules from Carcinogen-treated Rats¹

Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514 [J. G. C., S. J., R. G. T.], and Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27514 [J. A. P.]

The portal circulation of diethylnitrosamine-initiated nodules (0.5 to 7 mm in diameter) was studied in rat livers perfused exclusively via the portal vein. Microlight guides were placed on normal and nodular tissue on the capsular surface of the liver to measure pyridine nucleotide fluorescence (366 450 nm). When oxygen tension of the inflow perfusate was lowered, fluorescence in both normal tissue and small nodules (<2 mm in diameter) increased sharply due to the reduction of pyridine nucleotides, indicating previous normoxia. In contrast, similar manipulations did not increase fluorescence in nodules >2 mm in diameter, demonstrating that nicotinamide adenine dinucleotide was reduced maximally previously; i.e., the nodules were anoxic. Direct measurements of nodule oxygen concentrations with a miniature oxygen electrode confirmed these results. 7-Hydroxycoumarin or fluorescein could be detected with microlight guides in normal tissue and nodules <2 mm in diameter but not in nodules >2 mm in diameter. Furthermore, fluorescent microscopy indicated an absence of fluorescein in nodules >2 mm in diameter. Therefore, with four independent optical and polarographic techniques, we have demonstrated reduced portal circulation in nodules >2 mm in diameter; however, smaller nodules could not be differentiated from normal tissue.

¹ Supported in part by the Chemical Industry Institute of Toxicology.

² A Chemical Industry Institute of Toxicology predoctoral fellow.

³ Present address: Department of Pharmacology, Rutgers State University, Piscataway, N. J. 08854.

⁴ Recipient of Career Development Award AA-00033 and Grants CA-23080 and ES-02759. To whom requests for reprints should be addressed.

Received 1/13/83. Accepted 4/ 6/83.

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