Breast cancer 1 (BRCA1) protection in altered gene expression and neurodevelopmental disorders due to physiological and ethanol-enhanced reactive oxygen species formation.
Free Radic Biol Med
; 208: 272-284, 2023 11 01.
Article
en En
| MEDLINE
| ID: mdl-37541454
ABSTRACT
The breast cancer 1 (Brca1) susceptibility gene regulates the repair of reactive oxygen species (ROS)-mediated DNA damage, which is implicated in neurodevelopmental disorders. Alcohol (ethanol, EtOH) exposure during pregnancy causes fetal alcohol spectrum disorders (FASD), including abnormal brain function, associated with enhanced ROS-initiated DNA damage. Herein, oxidative DNA damage in fetal brains and neurodevelopmental disorders were enhanced in saline-exposed +/- vs. +/+ Brca1 littermates. A single EtOH exposure during gestation further enhanced oxidative DNA damage, altered the expression of developmental/DNA damage response genes in fetal brains, and resulted in neurodevelopmental disorders, all of which were BRCA1-dependent. Pretreatment with the ROS inhibitor phenylbutylnitrone (PBN) blocked DNA damage and some neurodevelopmental disorders in both saline- and EtOH-exposed progeny, corroborating a ROS-dependent mechanism. Fetal BRCA1 protects against altered gene expression and neurodevelopmental disorders caused by both physiological and EtOH-enhanced levels of ROS formation. BRCA1 deficiencies may enhance the risk for FASD.
Palabras clave
Alcohol (ethanol); Behavioural disorders; Breast cancer 1 susceptibility gene (Brca1); DNA damage; Executive function; Fetal alcohol spectrum disorders (FASD); Gene expression; Learning and memory; Motor coordination; Neurodevelopmental disorders; Reactive oxygen species (ROS); Repetitive behaviours
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastornos del Espectro Alcohólico Fetal
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Trastornos del Neurodesarrollo
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Neoplasias
Límite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA