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The study using wild-type andOgg1knockout mice exposed to potassium bromate shows no tumor induction despite an extensive accumulation of 8-hydroxyguanine in kidney DNA

Authors
Journal
Toxicology
0300-483X
Publisher
Elsevier
Publication Date
Volume
221
Identifiers
DOI: 10.1016/j.tox.2006.01.004
Keywords
  • Potassium Bromate (Kbro3)
  • Ogg1Knockout Mice
  • 8-Hydroxyguanine (8-Oh-G)
  • 8-Hydroxydeoxyguanosine (8-Oh-Dg)
  • Chronic Exposure
  • Carcinogenesis

Abstract

Abstract In order to assess the effect of potassium bromate (KBrO 3) on the induction of tumor formation, a 1-year carcinogenesis study was performed using Ogg1 knockout mice ( Ogg1 −/− ) and wild-type mice ( Ogg1 +/+ ). The mice were chronically exposed to KBrO 3 by putting it in the drinking water for 29 weeks, at 2 g/l for the first 18 weeks, and then at 1 g/l for another 11 weeks. After termination of treatment the mice were kept for an additional 23 weeks. The amount of 8-hydroxydeoxyguanosine (8-OH-dG) in kidney DNA after 29 weeks of KBrO 3 exposure reached 500 8-OH-dG/10 6 dG, almost 250-fold that of untreated wild-type mice. During the course of study the mice appeared normal, although a decrease of body weight gain in both Ogg1 −/− and Ogg1 +/+ mice exposed to KBrO 3, and some kidney malfunction in KBrO 3 treated Ogg1 −/− mice was observed. Surprisingly, when Ogg1 −/− and Ogg1 +/+ mice were sacrificed at 52 weeks, no tumor formation could be found in kidney or other organs such as lung, liver, spleen, thymus, stomach and intestine. Microscopic examination also showed the absence of precancerous foci in all tissues of both Ogg1 −/− and Ogg1 +/+ mice. A possible explanation is presented to reconcile these results with those of others which showed an increased incidence of tumor formation in untreated Ogg1 −/− mice.

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