Dietary D-glucarate effects on the biomarkers of inflammation during early post-initiation stages of benzo[a]pyrene-induced lung tumorigenesis in A/J mice

Robert Zoltaszek, Piotr Kowalczyk, Magdalena C. Kowalczyk, Margaret Hanausek, Zofia M. Kilianska, Thomas J. Slaga, Zbigniew Walaszek

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Previous studies showed that dietary calcium D-glucarate (CG) inhibited benzo[a]pyrene (B[a]P)-induced A/J mouse lung tumorigenesis, suppressing cell proliferation and chronic inflammation and inducing apoptosis during late post-initiation stages. The present study aimed to investigate changes in the homeostasis of cytokines in blood serum, as well as alterations in biomarkers of inflammation and apoptosis in lung tissue caused by dietary CG during early post-initiation stages of B[a]P-induced lung tumorigenesis. Two doses of 3 mg of B[a]P were given intragastrically to A/J mice 2 weeks apart. CG administration in the AIN-93G diet (2 and 4%, w/w) commenced at 2 weeks following the second dose of B[a]P. The levels of interleukin (IL)-6, IL-10 and tumor necrosis factor α (TNFα) in blood serum were investigated by FCAP array analysis. Two weeks after the second dose of B[a]P, approximately 8- and 28-fold increases of TNFα and IL-6, respectively, occurred in the blood serum and an approximately 16% decrease of IL-10 levels compared to the untreated control group was noted. At 4 weeks after the second dose of B[a]P and after 2 weeks of CG administration in the diet, the 2 and 4% CG diets significantly reduced the levels of IL-6 and TNFα (by 70 and 33%, respectively). In a dose-related manner, the diets also increased the level of anti-inflammatory cytokine IL-10 compared to the B[a]P group. At 6 weeks after the second dose of B[a]P, the cytokine levels in the serum continued to show a decrease in the CG-treated groups. These events are accompanied by an increased level of cleaved caspase-9 product with a molecular weight of 37kDa. In conclusion, dietary D-glucarate decreases the level of proinflammatory cytokines, increases the level of the anti-inflammatory cytokine IL-10 during early post-initiation stages of B[a]P-induced lung tumorigenesis in A/J mice and affects apoptotic induction.

Original languageEnglish (US)
Pages (from-to)145-154
Number of pages10
JournalOncology Letters
Volume2
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Apoptosis
  • Cytokines
  • Inflammation
  • Lung cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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