Chromosome intrachanges and interchanges detected by multicolor banding in lymphocytes: searching for clastogen signatures in the human genome.
Genomic fingerprints of mutagenic agents would have wide applications in the field of cancer biology, epidemiology and prevention. The differential spectra of chromosomal aberrations induced by different clastogens suggest that ratios of specific aberrations can be exploited as biomarkers of carcinogen exposure. We have tested this hypothesis using the novel technique of multicolor banding in situ hybridization (mBAND) in human peripheral blood lymphocytes exposed in vitro to X rays, neutrons, heavy ions, or the restriction endonuclease AluI. In the heavy-ion-irradiated cells, we further analyzed aberrations in chromosome 5 using multicolor FISH (mFISH). Contrary to the expectations of biophysical models, our results do not support the use of the ratios of inter-/intrachromosomal exchanges or intra-/interarm intrachanges as fingerprints of exposure to densely ionizing radiation. However, our data point to measurable differences in the ratio of complex/simple interchanges after exposure to different clastogens. These data should be considered in current biophysical models of radiation action in living cells.
Johannes
C
C
Department of Genetics, University of Duisburg-Essen, 45117 Essen, Germany.
Horstmann
M
M
Durante
M
M
Chudoba
I
I
Obe
G
G
D015415:Biomarkers / Q000097:blood*; D002869:Chromosome Aberrations / Q000145:classification / Q000528:radiation effects*; D002871:Chromosome Banding / Q000379:methods*; D002875:Chromosomes / Q000528:radiation effects*; D016172:DNA Fingerprinting / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000528:radiation effects*; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000528:radiation effects*; D009153:Mutagens / Q000494:pharmacology; D011829:Radiation Dosage
D015415:Biomarkers; D005819:Genetic Markers; D009153:Mutagens; C024669:endodeoxyribonuclease AluI; D015252:Deoxyribonucleases, Type II Site-Specific