The PKZ1 Recombination Mutation Assay: A Sensitive Assay for Low Dose Studies

Sykes, P. J.; Morley, A. A.; Hooker, A. M.
April 2006
Dose-Response;2006, Vol. 4 Issue 2, p91
Academic Journal
The majority of mutation studies are performed at high doses of DNA damaging agents due to the insensitivity of most mutation assays. Extrapolation using a linear no-threshold (LNT) dose response model is then used to estimate the extent of possible DNA damage at lower doses. There is increasing evidence to suggest that the LNT model may not be correct at low doses of at least some DNA damaging agents. The pKZ1 in vivo and in vitro recombination assays have proven to be very sensitive for detection of changes in chromosomal inversion in lymphoid tissue in response to low doses of DNA damaging agents. Non-linear dose response curves for chromosomal inversion as an end-point have been identified at low doses of DNA damaging agents using this assay. Here, we review the inversion results obtained to date with the pKZ1 assays and discuss their suitability for low dose studies.


Related Articles

  • Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage. Pollycove, Myron; Feinendegen, Ludwig E // Human & Experimental Toxicology;Jun2003, Vol. 22 Issue 6, p290 

    Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation...

  • In Vivo Mutagenic Effect of Very Low Dose Radiation. Sykes, Pamela J.; Day, Tanya K.; Swinburne, Sarah J.; Lane, Joanne M.; Morley, Alexander A.; Hooker, Antony M.; Bhat, Madhava // Dose-Response;2006, Vol. 4 Issue 4, p309 

    Almost all of our knowledge about the mutational effect of radiation has come from high dose studies which are generally not relevant to public exposure. The pKZ1 mouse recombination mutagenesis assay enables study of the mutational effect of very low doses of low LET radiation (μGy to cGy...

  • The miR-99 family regulates the DNA damage response through its target SNF2H. Mueller, A C; Sun, D; Dutta, A // Oncogene;2/28/2013, Vol. 32 Issue 9, p1164 

    Chromatin remodeling factors are becoming known as crucial facilitators of recruitment of repair proteins to sites of DNA damage. Multiple chromatin remodeling protein complexes are now known to be required for efficient double strand break repair. In a screen for microRNAs (miRNAs) that...

  • Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Wei, Min; Shinkura, Reiko; Doi, Yasuko; Maruya, Mikako; Fagarasan, Sidonia; Honjo, Tasuku // Nature Immunology;Mar2011, Vol. 12 Issue 3, p264 

    To elucidate the specific role of somatic hypermutation (SHM) in mucosal immunity, we generated mice carrying a knock-in point mutation in Aicda, which encodes activation-induced cytidine deaminase (AID), an enzyme essential to SHM and class-switch recombination (CSR). These mutant AIDG23S mice...

  • BCL10 is not the gene inactivated by mutation in the 1p22 deletion region in mantle cell lymphoma. Bullinger, L; Leupolt, E; Schaffner, C; Mertens, D; Bentz, M; Lichter, P; Döhner, H; Stilgenbauer, S // Leukemia (08876924);Aug2000, Vol. 14 Issue 8, p1490 

    The BCL10 gene has recently been cloned from the 1p22 breakpoint of the translocation t(1;14)(p22;q32) observed in mucosa-associated lymphoid tissue (MALT) lymphoma. BCL10 was shown to be a proapoptotic-signaling gene encoding a protein that contains an amino-terminal caspase recruitment domain...

  • Genomic technology: Recombination maps get personal. Burgess, Darren J. // Nature Reviews Genetics;Sep2012, Vol. 13 Issue 9, p597 

    The article discusses research which used a single-cell augmentation approach for the generation on recombination maps, which references the study "Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm," by J. Wang and colleagues in the 2012 issue.

  • The pattern of neutral molecular variation under the background selection model. Charlesworth, D.; Charlesworth, B. // Genetics;Dec95, Vol. 141 Issue 4, p1619 

    Studies the behavior of genetic diversity at a neutral locus in a genomic region without recombination but subject to selection against deleterious alleles maintained by recurrent mutation. Effect of background selection on the number of segregating sites; Examination of the power of tests for...

  • The effects of insertions on mammalian intrachromosomal recombination. Godwin, Alan R.; Liskay, R. Michael // Genetics;Feb94, Vol. 136 Issue 2, p607 

    Examines the effects of insertion mutations on intrachromosomal recombination. Recombination rates; Analysis of direct repeat recombinants; Analysis of inverted repeat recombinants; Exceptional inverted repeat recombinants; Summary of recombinant analysis.

  • A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior. Leonard, Bobby E. // Dose-Response;2008, Vol. 6 Issue 2, p113 

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics