Adverse Outcome Pathway on Alkylation of DNA in Male Pre-Meiotic Germ Cells Leading to Heritable Mutations

Carole Yauki ; Iain Lambertii ; Francesco Marchettii ; George Douglasi iEnvironmental Health Science ; Research Bureau ; Health CanadaiiCarleton University

Organisation for Economic Co-operation and Development

关键词: DNA adducts;    DNA alkylation;    DNA repair;    heritable mutations;    male pre-meiotic germ cells;   

DOI  :  https://doi.org/10.1787/5jlsvvxn1zjc-en

学科分类：社会科学、人文和艺术（综合）

来源: OECD iLibrary

【 摘 要 】

Germ cell/heritable mutations are important regulatory endpoints for international agencies interested in protecting the health of future generations. However, germ cell mutation analysis has been hampered by a lack of efficient tools. The motivation for developing this AOP was to provide context for new assays in this field, identify research gaps and facilitate the development of new methods. In this AOP, a compound capable of alkylating DNA is delivered to the testes causing germ cell mutations and subsequent mutations in the offspring of the exposed parents. Although there are some gaps surrounding some mechanistic aspects of this AOP, the overarching AOP is widely accepted and applies broadly to any species that produces sperm.