Mutational signatures in T-lymphocytes of rats treated with N-propyl-N-nitrosourea and procarbazine.
Environ Mol Mutagen
; 62(6): 350-363, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-34117657
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 CâT transition with all other single base substitutions evenly distributed. The PNU-induced mutational signature showed relatively equal contributions from CâT and TâC transitions, and TâA transversions. The PCZ-induced signature was characterized by TâC transitions, TâA and, to a smaller extent, TâG transversions. CâG 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 risk assessment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Procarbazina
/
Linfócitos T
/
Regulação da Expressão Gênica
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Mutação
/
Compostos de Nitrosoureia
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Environ Mol Mutagen
Assunto da revista:
BIOLOGIA MOLECULAR
/
SAUDE AMBIENTAL
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos