\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{The Fertilized Avian Egg Fetal Liver Assays for Assessing DNA Damaging
Potential of Chemicals: A Comparative Analysis with In Vitro and In Vivo
Genotoxicity Assays and Rodent Carcinogenicity}



\author[1]{Tetyana Kobets}%
\author[1]{Gary Williams}%
\affil[1]{New York Medical College}%


\vspace{-1em}



  
  \date{March 17, 2025}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
The ability to produce direct DNA damage (genotoxicity) underlies the
carcinogenic mode of action of various chemicals. As such, genotoxicity
endpoints are typically evaluated in a regulatory-approved battery of in
vitro tests with potential in vivo follow-up. Growing concern for animal
welfare and implementation of new regulations which restrict the use of
laboratory animals necessitated the introduction of New Approach
Methodologies (NAMs). The avian egg-based (in ovo) models, the Chicken
and related Turkey Egg Fetal Liver DNA Damage Assays, were developed as
metabolically competent NAMs to potentially replace short-term in vivo
genotoxicity assays for chemicals that are genotoxic in vitro. Both
models utilize avian fetal livers for the evaluation of endpoints
indicative of DNA damage produced by either direct or indirect
mechanisms, specifically, the formation of nuclear DNA adducts and
strand breaks. Moreover, avian embryos carry genetic and morphologic
resemblance to mammals and can be used for an extensive evaluation of
other endpoints including histopathology and tissue-specific genomic
profiling. Avian fetal livers contain a full complement of metabolizing
enzymes and are capable of bioactivation, detoxication, and elimination
of xenobiotics. The comprehensive analysis of 87 and 59 chemicals
assessed in the chicken and turkey models, respectively, revealed a
stronger correlation with the results from in vivo assays demonstrating
that in ovo models can detect the genotoxic potential of a broader range
of compounds compared to in vitro assays with S9 supplementation. In
conclusion, fertilized avian egg fetal liver assays offer a promising
alternative to traditional in vivo genotoxicity assays.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`Detection of chemical DNA damage in avian fetal livers.docx`  available at \url{https://authorea.com/users/815312/articles/1252569-the-fertilized-avian-egg-fetal-liver-assays-for-assessing-dna-damaging-potential-of-chemicals-a-comparative-analysis-with-in-vitro-and-in-vivo-genotoxicity-assays-and-rodent-carcinogenicity}

\selectlanguage{english}
\FloatBarrier
\end{document}

