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The Use of Human Lung Slices in Toxicology

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona

Mary S. Smith

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona, The Procter and Gamble Company, Ivorydale Technical Center, Cincinnati, Ohio, USA

Steven J. Hasal

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona

Katherine S. Hasal

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona

A. Jay Gandolfi

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona

Klaus Brendel

Department of Pharmacology, Health Sciences Center, University of Arizona, Tucson, Arizona

1 Successful use of agar-filled precision-cut rat lung slices in dynamic organ culture prompted the use of this technology with human lung.

2 The larger tissue mass of a human lung required that the trachea be cannulated with a balloon catheter and subsequently inflated with 4 liters of warm agar/medium mixture and then cooled before being precision-cut into 500 µm thick slices.

3 To characterize the human lung slices, viability and the effects of acrolein and nitrofurantoin were assessed over a period of 24 h using protein synthesis and nonprotein sulfhydryl content.

4 Control human lung slices synthesized protein at a linear rate and maintained a stable nonprotein sulfhydryl content for 24 h.

5 Slices incubated with acrolein exhibited no significant decrease in protein synthesis or nonprotein sulfhydryl levels until 24 h.

6 Incubation with nitrofurantoin exhibited a definite time- and dose-dependent inhibition of protein synthesis, and depletion of the cellular thiol pool.

7 These results indicate that this human lung tissue slice system may be used as an in vitro model to identify and screen pneumotoxicants.

Human & Experimental Toxicology, Vol. 13, No. 7, 466-471 (1994)
DOI: 10.1177/096032719401300703


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