The accumulation of putrescine and paraquat into lung slices taken from BHT treated mice.
Putrescine and paraquat have been shown to accumulate in slices of mouse lung by a process which obeys saturation kinetics. The Vmax for the process was similar for both compounds (1.18 and 1.29 mumol/g wet wt/h) although the apparent Km for putrescine was 15 microM compared with 209 microM for paraquat. Mice were given a range of doses of BHT (i.p.) and the sequence and nature of the changes in morphology of the lung determined by light and electron microscopy. Lung slices were prepared from mice given BHT, and their ability to accumulate both paraquat and putrescine was determined. Within 4 days of dosing with 200 mg BHT/kg, there was marked cellular proliferation in the lung with an increase in the number of type II epithelial cells. Seven days after dosing the lungs had generally returned to their normal morphology with only occasional areas in some lungs showing evidence of damage. Between 1 day and 7 days after dosing, slices of mouse lung showed a reduced ability to accumulate paraquat or putrescine. This did not return to control values until 14 days. The greatest reduction in the accumulation of either compound was seen 4 days after dosing when the proliferation of the type II epithelial cells was most marked. Mice given 150 mg BHT/kg showed similar but less extensive morphological change and the ability of lung cells from these mice to accumulate paraquat or putrescine was not as severely reduced compared with mice given 200 mg BHT/kg. With doses of 100 mg BHT/kg the accumulation of paraquat and putrescine was only slightly reduced and there was a correspondingly minimal affect on lung morphology. The lungs of mice given 50 mg BHT/kg were unaffected as was their ability to accumulate either compound. The results from this study, when taken in the context of previously reported data, support the conclusion that paraquat is accumulated into the lung by a process responsible for the uptake of putrescine. In the rat, paraquat and putrescine are known to accumulate in alveolar type II cells and therefore it appears that the regenerating alveolar type II epithelial cell is functionally unable to accumulate these compounds and may be considered physiologically similar to type II epithelial cells in immature animals.
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010269:Paraquat / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects; D011700:Putrescine / Q000378:metabolism*; D013997:Time Factors
D002084:Butylated Hydroxytoluene; D010269:Paraquat; D011700:Putrescine