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Titolo:
Quantification of illegitimate V(D)J recombinase-mediated mutations in lymphocytes of newborns and adults
Autore:
Scheerer, JB; Xi, LQ; Knapp, GW; Setzer, RW; Bigbee, WL; Fuscoe, JC;
Indirizzi:
US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA US EPARes Triangle Pk NC USA 27711 enesis, Res Triangle Pk, NC 27711 USA Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 xicol, Chapel Hill, NC 27599 USA Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15238 USA Univ Pittsburgh Pittsburgh PA USA 15238 at Hlth, Pittsburgh, PA 15238 USA US EPA, Res & Adm Support Div, Res Triangle Pk, NC 27711 USA US EPA Res Triangle Pk NC USA 27711 rt Div, Res Triangle Pk, NC 27711 USA Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA Univ Pittsburgh Pittsburgh PA USA 15261 idemiol, Pittsburgh, PA 15261 USA Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA Univ Pittsburgh Pittsburgh PA USA 15213 st Canc, Pittsburgh, PA 15213 USA
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 2, volume: 431, anno: 1999,
pagine: 291 - 303
SICI:
1386-1964(199912)431:2<291:QOIVRM>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOLLICULAR LYMPHOMA; PERIPHERAL-BLOOD; T-LYMPHOCYTES; HPRT GENE; B-CELLS; CHROMOSOMAL BREAKPOINT; CORD-BLOOD; T(14-18); HUMANS; LOCUS;
Keywords:
V(D)J recombination; HPRT; t(14;18) translocation; BCL-2; molecular sequence data; polymerase chain reaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Fuscoe, JC US EPA, Div Environm Carcinogenesis, Mail Drop 68, Res TrianglePk, NC 27711 USA US EPA Mail Drop 68 Res Triangle Pk NC USA 27711 , NC 27711 USA
Citazione:
J.B. Scheerer et al., "Quantification of illegitimate V(D)J recombinase-mediated mutations in lymphocytes of newborns and adults", MUT RES-F M, 431(2), 1999, pp. 291-303

Abstract

We used a direct polymerase chain reaction (PCR) method for quantificationof HPRT exons 2+3 deletions and t(14:18) translocations as a measure of illegitimate V(D)J recombination. We determined the baseline frequencies of these two mutations in mononuclear leukocyte DNA from the umbilical cord blood of newborns and from the peripheral blood of adults, In an initial groupof 21 newborns, no t(14;18) translocations were detected (< 0.049 X 10(-7)). The frequency of HPRT exons 2 + 3 deletions was 0.10 X 10(-7) per mononuclear leukocyte, lower than expected based on the T-cell proportion of thiscell fraction (55%-70%) and previous results using the T-cell cloning assay (similar to 2-3 X 10(-7) per clonable T-cell), Phytohemagglutinin (PHA), as used in the T-cell cloning assay, was examined for its effect on the frequencies of these mutation events in mononuclear leukocytes from an additional 11 newborns and from 12 adults. There was no significant effect of PI-Won t(14;18) translocations which were rare among the newborns (1 detected among 2.7 X 10(8) leukocytes analyzed), and which occurred at frequencies from < 1 X 10(-7) (undetected) to 1.6 X 10(-4) among the adults. The extremely high frequencies of t(14;18)-bearing cells in three adults were due mainly to in vivo expansion of two to six clones. However. PHA appeared to stimulate a modest (although not significant) increase in the frequency of HPRTexons 2 + 3 deletions in the leukocytes of the newborns, from 0.07 X 10(-7) to 0.23 X 10(-7). We show that both the direct PCR assay and the T-cell cloning assay detect similar frequencies of HPRT exons 2 + 3 deletions when calculations are normalized to blood volume, indicating that the apparent discrepancy is probably due to the different population of cells used in theassays. This direct PCR assay may have utility in characterizing the effects of environmental genotoxic agents on this clinically important recombination mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 01:09:04