Mutational signatures in T-lymphocytes of rats treated with N-propyl-N-nitrosourea and procarbazine.

Environmental and Molecular Mutagenesis
Javier R RevolloVasily N Dobrovolsky

Abstract

We have used whole genome sequencing (WGS) to determine mutational signatures induced in the T-cells of rats treated in vivo with N-propyl-N-nitrosourea (PNU) or procarbazine (PCZ). The signatures from the treated rats were different from the signature of background mutations. The main component of the spontaneous T-cell mutational signature was C➔T transition with all other single base substitutions evenly distributed. The PNU-induced mutational signature showed relatively equal contributions from C➔T and T➔C transitions, and T➔A transversions. The PCZ-induced signature was characterized by T➔C transitions, T➔A and, to a smaller extent, T➔G transversions. C➔G transversions were infrequent in either the PNU or PCZ signatures. WGS not only allowed mutational signature detection, but also measured quantitative responses to mutagen treatment: 10-40× increases in the number of mutations per clone were detected in T-cell clones from treated rats. The overall strand specificity of induced mutations for annotated rat genes was comparable to the strand specificity of mutations determined previously for the endogenous X-linked Pig-a gene. Our results provide valuable reference data for future applications of WGS in safety research and r...Continue Reading

References

Jan 1, 1978·Mutation Research·I P Lee, R L Dixon
Jan 1, 1991·Environmental and Molecular Mutagenesis·B C Myhr
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J A GossenJ Vijg
Sep 1, 1987·Mutation Research·J B Guttenplan
Dec 1, 1973·Environmental Health Perspectives·B N Ames
Jan 1, 1996·Environmental and Molecular Mutagenesis·P J StambrookJ A Tischfield
Oct 20, 1998·Nucleic Acids Research·P P Van SlounH Vrieling
Feb 25, 1999·Mutation Research·V N DobrovolskyR H Heflich
Oct 24, 2001·Mutation Research·R J Albertini
Aug 6, 2005·Mutation Research·Iain B LambertGeorge R Douglas
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Nov 30, 2011·Current Molecular Pharmacology·Jihong ZhangTracey D Bradshaw
May 9, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·B Bhaskar GollapudiJennifer Y Tanir
Dec 14, 2017·Mutagenesis·Javier RevolloVasily N Dobrovolsky
May 1, 2018·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Javier R RevolloVasily N Dobrovolsky
Jun 8, 2018·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Young-Shin ChungJong-Kwon Lee
Apr 16, 2019·Cell·Jill E KucabSerena Nik-Zainal
Apr 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Lei ZhangJan Vijg
Sep 4, 2019·BMC Bioinformatics·Franziska SchumannDieter Beule
Oct 11, 2019·Environmental and Molecular Mutagenesis·Robert H HeflichPaul A White
Oct 28, 2019·Nature·Henry Lee-SixMichael R Stratton
Dec 16, 2020·Proceedings of the National Academy of Sciences of the United States of America·Charles C ValentineJesse J Salk

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