Abstract
Recent changes in the risk assessment landscape underscore the need to be able to compare the results of toxicity and dose-response testing between a growing list of animal models and, quite possibly, an array of in vitro screening assays. How do we compare test results for a given compound between vastly different species? For example, what dose level in the ambient water of a small fish model would be equivalent to 10 ppm of a given compound in the rat's drinking water? Where do we begin? To initially address these questions, and in order to compare dose-response tests in a standard rodent model with a fish model, we used the concept of molecular dose. Assays that quantify types of DNA damage that are directly relevant to carcinogenesis integrate the factors such as chemical exposure, uptake, distribution, metabolism, etc. that tend to vary so widely between different phyletic levels. We performed parallel exposures in F344 rats and Japanese medaka (Oryzias latipes) to the alkylating hepatocarcinogen, dimethylnitrosamine (DMN). In both models, we measured the DNA adducts 8-hydroxyguanine, N(7)-methylguanine and O(6)-methylguanine in the liver; mutation frequency using lambda cII transgenic medaka and lambda cII transgenic (Bi...Continue Reading
References
Aug 1, 1987·Carcinogenesis·Y NakatsuruT Ishikawa
Oct 1, 1995·Carcinogenesis·V L SouliotisS A Kyrtopoulos
Mar 1, 1993·Mutation Research·K AokiT Ishikawa
Jan 1, 1995·Environmental and Molecular Mutagenesis·G J Carr, N J Gorelick
May 1, 1993·Mutagenesis·J C MirsalisJ M Short
Sep 1, 1996·Mutation Research·D K La, J A Swenberg
Nov 14, 1997·Regulatory Toxicology and Pharmacology : RTP·R J GoldenE A Reese
Apr 3, 1998·Carcinogenesis·J M LawJ A Swenberg
Jul 11, 1998·Carcinogenesis·V L SouliotisS A Kyrtopoulos
Jul 22, 1998·Mutation Research·G S BaileyJ D Hendricks
Nov 4, 1998·Mutagenesis·D E WatsonK R Tindall
Jun 5, 1999·Carcinogenesis·M S Okihiro, D E Hinton
May 30, 2001·Mutation Research·T IshikawaY Nakatsuru
Oct 3, 2001·ILAR Journal·J M Law
Oct 3, 2001·ILAR Journal·R N Winn
Mar 14, 2002·Toxicologic Pathology·R Julian Preston
Mar 14, 2002·Mutation Research·Vassilis L SouliotisSoterios A Kyrtopoulos
Mar 20, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·David R GeterWilliam E Hawkins
Nov 16, 2004·Mutation Research·Vassilis L SouliotisSoterios A Kyrtopoulos
Dec 18, 2004·Toxicologic Pathology·Igor V MizgireuvSergei Y Revskoy
May 10, 2005·Environmental and Molecular Mutagenesis·Richard N WinnMichelle B Norris
Citations
Oct 16, 2010·PloS One·Lingling DingWilliam S Dynan
May 2, 2014·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Alaa El-Din Hamid SayedHiroshi Mitani
Jan 20, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·David E HintonJeffrey A Yoder
Feb 2, 2010·Environmental and Molecular Mutagenesis·Tonya L WardKathleen A Hill
May 21, 2016·Journal of Photochemistry and Photobiology. B, Biology·Alla El-Din Hamid SayedHiroshi Mitani
Jul 5, 2011·Veterinary Pathology·K R HobbieJ M Law
Jul 3, 2010·Medicine, Health Care, and Philosophy·Shawn H E Harmon
Feb 9, 2017·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takehiko NohmiNaomi Toyoda-Hokaiwado
Nov 27, 2020·Journal of Toxicologic Pathology·Yumiko HoshikawaAkihiko Sugiyama