Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism

Yihong Cao, Jiang Wang, Ronda Henry-Tillman, Vicki Klimberg

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. One mechanism of the mammary carcinogenesis of 7,12-dimethylbenz[a]anthracene (DMBA) is thought to be the generation of reactive oxygen species known to play an important role in initiation and progression. We hypothesized that DMBA would disrupt gut glutathione (GSH) metabolism and this disruption would correlate with mammary cell carcinogenesis. Methods. Sixty-four Sprague - Dawley rats were randomized to the DMBA versus control groups. At age 50 days, rats were gavaged with a one-time dose of 20 mg DMBA or sesame oil. Rats from each group were sacrificed at 1 week (n = 16), 2 weeks (n = 16), 4 weeks (n = 16), and 11 weeks (n = 16). Tumor appearance, arterial and gut GSH concentration, and gut GSH extraction were measured over time. Results. Gut GSH extraction (normally negative; production) was significantly depressed over the time points, even showing uptake (positive extraction) at Weeks 1 and 2. Tumors developed in all animals in the DMBA group by Week 11. Conclusions. A one-time oral administration of DMBA has a significant and prolonged depressive effect on gut GSH production that has not previously been described. These data support the hypothesis that the carcinogenic effect of DMBA is mediated, at least in part, by oxidative damage and that the disruption of gut GSH metabolism may play a greater role in carcinogenesis than previously realized.

Original languageEnglish (US)
Pages (from-to)135-140
Number of pages6
JournalJournal of Surgical Research
Volume100
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

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9,10-Dimethyl-1,2-benzanthracene
Glutathione
Carcinogenesis
Breast
Sesame Oil
anthracene
Oral Administration
Sprague Dawley Rats
Reactive Oxygen Species
Neoplasms
Control Groups

Keywords

  • 7,12-Dimethylbenz[a] anthracene (DMBA)
  • Glutathione gut production

ASJC Scopus subject areas

  • Surgery

Cite this

Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism. / Cao, Yihong; Wang, Jiang; Henry-Tillman, Ronda; Klimberg, Vicki.

In: Journal of Surgical Research, Vol. 100, No. 1, 2001, p. 135-140.

Research output: Contribution to journalArticle

Cao, Yihong ; Wang, Jiang ; Henry-Tillman, Ronda ; Klimberg, Vicki. / Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism. In: Journal of Surgical Research. 2001 ; Vol. 100, No. 1. pp. 135-140.
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