Wednesday, September 14, 2011

Reviewing the historical Journal literature for publications discussing Cancer risk associated with joint/hip implants (9 of 9)

I would like to close this series with a NEW publication in 2011.  I found it fascinating.

Some definitions are in order as usual before plunging into this abstract:

What the heck is  drosophila melansogaster? Fruit fly!

Drosophila melanogaster (Greek for dark-bellied dew lover : δρόσος = dew, φίλος = intimate friend, lover, μέλας = dark-coloured, γαστήρ = belly[2]) is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is commonly known as the common fruit fly or vinegar fly. Starting from Charles W. Woodworth, this species is one of the most commonly used model organisms in biology, including studies in genetics, physiology, microbial pathogenesis and life history evolution because they are easy to take care of, breed quickly, and lay many  eggs.

You might ask why I reprinted this after reading it so let me tell you why up front.  As you know from previous work and studies that have been reprinted here, there have been nore than enough questions raised about whether in fact the current alleged non toxic chromium 3 is nothing more than chromium 6 (Toxic form) oxidized to chromium 3. One example of this can be found in its entirety at this link:

There is good evidence from the clinic and the laboratory that Cr[VI] is the ion responsible for most of the toxic actions, although much of the underlying molecular damage may be due to its intracellular reduction to the even more highly reactive and short-lived chemical species Cr[III] and Cr[V]. Exposure to Cr[VI] can result in various point mutations in DNA and to chromosomal damage, as well as to oxidative changes in proteins and to adduct formation. The relative importance of these effects of chromium ions and of the free oxidising radicals they may generate in the body in causing tumours and allergic sensitisation remain to be demonstrated. Biochemical studies of the DNA-damaging effects and of the pathogenesis of the allergic reactions to chromium ions have not kept up with advances in understanding of the molecular basis of the effects of other carcinogens and allergens.

Another definition is in order as well prior to reading this doc:

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day.[1] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages.[2][3]
The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:
  1. an irreversible state of dormancy, known as senescence
  2. cell suicide, also known as apoptosis or programmed cell death
  3. unregulated cell division, which can lead to the formation of a tumor that is cancerous

ok here you go!

Mutat Res. 2011 May 18;722(1):44-51. Epub 2011 Mar 5.

Tracing the tracks of genotoxicity by trivalent and hexavalent chromium in Drosophila melanogaster.


Embryotoxicology Section, Indian Institute of Toxicology Research, Lucknow 226 001, India.


Mutagen sensitive strains (mus) in Drosophila are known for their hypersensitivity to mutagens and environmental carcinogens. Accordingly, these mutants were grouped in pre- and post-replication repair pathways. However, studying mutants belonging to one particular repair pathway may not be adequate for examining chemical-induced genotoxicity when other repair pathways may neutralize its effect. To test whether both pre-and post-replication pathways are involved and effect of Cr(III)- and Cr(VI)-induced genotoxicity in absence or presence of others, we used double mutant approach in D. melanogaster. We observed DNA damage as evident by changes in Comet assay DNA migration in cells of larvae of Oregon R(+) and single mutants of pre- (mei-9, mus201 and mus210) and post- (mei-41, mus209 and mus309) replication repair pathways and also in double mutants of different combinations (pre-pre, pre-post and post-post replication repair) exposed to increasing concentrations of Cr(VI) (0.0, 5.0, 10.0 and 20.0 μg/ml) for 48 h. The damage was greater in pre-replication repair mutants after exposure to 5.0 μg/ml Cr(VI), while effects on Oregon R(+) and post replication repair mutants were insignificant. Post-replication repair mutants revealed significant DNA damage after exposure to 20.0 μg/ml Cr(VI). Further, double mutants generated in the above repair categories were examined for DNA damage following Cr(VI) exposure and a comparison of damage was studied between single and double mutants. Combinations of double mutants generated in the pre-pre replication repair pathways showed an indifferent interaction between the two mutants after Cr(VI) exposure while a synergistic interaction was evident in exposed post-post replication repair double mutants. Cr(III) (20.0 μg/ml) exposure to these strains did not induce any significant DNA damage in their cells. The study suggests that both pre- and post-replication pathways are affected in Drosophila by Cr(VI) leading to genotoxicity, which may have consequences for metal-induced carcinogenesis.

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