Monday, August 1, 2011

Chromium 3 results in permanent modification to DNA in MoM hip? (3 of 6.) What does this mean?

I would like to understand what it means when they say that "direct binding of Cr3 to DNA is well documented" and why this matters to us as patients.
  • Wolf et al 1989 (done in prior post)
  • Landon et al 2004
  • Bacon et al 1983
  • Martnett  et al 1999
  • Hartwig et al 2003
I will explore this in a series of 6 posts.

Background to the  Martnett journal article below

Metal-induced intracellular effects:
  • Chromium 6 is oxidized to Cr 3
  • Reactions with metal ions can lead to generation of free radicals which can cause cellular dysfunction.
  • Free radicals catalyze the oxidation of protein and phosoholipids ( a process known as lipid peroxidation.)  Lipid peroxidation leads to the formation of malondialdehyde which can react with DNA base.
  • Permanent modification of the genetic material resulting from this "oxidative damage" represents the first step in mutagenesis, carcinogenesis and ageing.

Mutat Res. 1999 Mar 8;424(1-2):83-95.

Lipid peroxidation-DNA damage by malondialdehyde.


A.B. Hancock Jr. Memorial Laboratory for Cancer Research Center in Molecular Toxicology, Vanderbilt Cancer Center, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville TN 37232, USA.


Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis that is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is a pyrimidopurinone called M1G. Site-specific mutagenesis experiments indicate that M1G is mutagenic in bacteria and is repaired by the nucleotide excision repair pathway. M1G has been detected in liver, white blood cells, pancreas, and breast from healthy human beings at levels ranging from 1-120 per 108 nucleotides. Several different assays for M1G have been described that are based on mass spectrometry, 32P-postlabeling, or immunochemical techniques. Each technique offers advantages and disadvantages based on a combination of sensitivity and specificity. Application of each of these techniques to the analysis of M1G is reviewed and future needs for improvements are identified. M1G appears to be a major endogenous DNA adduct in human beings that may contribute significantly to cancer linked to lifestyle and dietary factors. High throughput methods for its detection and quantitation will be extremely useful for screening large populations.

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