These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Effects of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on human small airway epithelial cells and the protective effects of myo-inositol.
    Author: Jyonouchi H, Sun S, Iijima K, Wang M, Hecht SS.
    Journal: Carcinogenesis; 1999 Jan; 20(1):139-45. PubMed ID: 9934861.
    Abstract:
    Benzo[a]pyrene (B[a]P), a tobacco-derived carcinogen, induces lung tumors in rodents through its carcinogenic metabolite, anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE). Tumorigenesis is inhibited by dietary myo-inositol in the post-initiation phase. However, little is known about how B[a]PDE and myo-inositol affect normal human lung cells. We addressed this question using untransformed human small airway epithelial (SAE) cells. SAE cell viability decreased <50% in parallel to an increase of apoptotic cells (>20%) 2 days after the cells were treated for 1 h with B[a]PDE (>100 nM). In contrast, the cell number and viability were not altered in A549 human lung cancer cells by B[a]PDE treatment up to 10 microM with <5% apoptotic cells and <10 U/l LDH in the medium. SAE cells retain the features of basal cells in serum-free, low Ca2+ (4 nM) medium up to 4-5 passages, but in serum-supplemented or serum-free, high Ca2+ (1 mM) cultures, they differentiate into non-ciliated epithelial cells expressing Clara cell secretory protein (CCSP). A non-toxic, physiologically relevant dose of B[a]PDE (1 nM) partially inhibited serum and Ca2+-induced SAE cell differentiation. This effect was abolished by wortmannin, a phosphatidylinositol-3 kinase (PI-3K) inhibitor, and PD98059, a mitogen activated protein kinase (MAPK) kinase-1 (MEK1) inhibitor, but not by SB202190, a p38 MAPK inhibitor, or melittin, a protein kinase C inhibitor. Myo-inositol (10-100 microM) did not alter growth or differentiation of untreated SAE or A549 cells, but reversed the inhibitory effect of B[a]PDE on serum and Ca2+-induced SAE cell differentiation when supplemented to the culture after B[a]PDE treatment. This myo-inositol action was not altered by PD98059, wortmannin or melittin, but was partially suppressed by SB202190. Collectively, these results indicate that B[a]PDE inhibits serum-induced SAE cell differentiation, possibly involving activating signals through a PI-3K/MEK1 mediated MAPK pathway, whereas myo-inositol protects SAE cells against this inhibitory effect of B[a]PDE perhaps through both PI-3K/MEK1 and p38 MAPK pathways.
    [Abstract] [Full Text] [Related] [New Search]