The use of human lung slices in toxicology.
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 microns 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.
Fisher
R L
RL
Department of Pharmacology, University of Arizona, Tucson 85724.
Smith
M S
MS
Hasal
S J
SJ
Hasal
K S
KS
Gandolfi
A J
AJ
Brendel
K
K
D000171:Acrolein / Q000633:toxicity; D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D046508:Culture Techniques; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009582:Nitrofurantoin / Q000633:toxicity; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014116:Toxicology / Q000379:methods*
D011506:Proteins; D013438:Sulfhydryl Compounds; D000171:Acrolein; D009582:Nitrofurantoin