Y. Morimoto et al., Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers, INHAL TOXIC, 13(7), 2001, pp. 589-601
To investigate whether the results of intratracheal instillation studies on
mineral fibers reflect the findings obtained by long-term inhalation data
on mineral fibers, we have examined gene expression of cytokines and pathol
ogical features in lungs induced by intratracheal instillation and inhalati
on of mineral fibers. Male Wistar rats were given a single intratracheal in
stillation of 2 mg alumina silicate refractory fiber (RF1) or potassium oct
atitanate whisker ( PT1), and were sacrificed 4 wk after the fiber instilla
tion. Longterm inhalation studies were also performed. In these, animals we
re exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacri
ficed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (
TNF-alpha), interleukin-6 ( IL-6), and transforming growth factor-beta1 ( T
GF-beta1) from lungs was observed by reverse-transcription polymerase chain
reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA i
n PT1-exposed lung was significantly higher than for those exposed to RF1 i
n both intratracheal instillation and inhalation studies. Pathological find
ings revealed that mild pulmonary fibrosis was seen in the lungs after intr
atracheal instillation and inhalation of PT1 but not RF1. Similarities were
observed not only in gene expression of cytokines but in pathological feat
ures between both studies. These data suggested that the results of intratr
acheal instillation reflect the findings obtained from long-term inhalation
data.