Dose-response relationship for rat liver DNA damage caused by 1,2-dimethylhydrazine

Toxicology
K T Kitchin, J L Brown

Abstract

An experimental approach was taken to the question of dose-response curves for chemical carcinogenesis, using DNA damage as a biomarker. Female rats were give 13 different doses of 1,2-dimethylhydrazine (from 1.4 to 135,000 micrograms/kg) and the subsequent hepatic DNA damage was determined by the alkaline elution technique. DMH doses below 450 micrograms/kg did not significantly damage DNA; all DMH doses of 1000 micrograms/kg or higher damaged rat hepatic DNA (P < 0.05). In this study the x values (dose) ranged over five orders of magnitude and the y values (DNA damage) ranged 30-fold. Ten different regression models (linear, quadratic, cubic, power, and six nonlinear transition models) were compared in their ability to fit the experimental data. With respect to log transformed dose, the six nonlinear transition equations fit the data considerably better than the four power type of equations. A sigmoid model fit to the log transformed dose of 1,2-dimethylhydrazine had an r2 of 0.9979, a degree of freedom adjusted r2 of 0.9969, a F-statistic of 1,457, and a fit standard error of 0.50. With respect to untransformed dose, only three equations (sigmoid, cascade and gaussian cumulative) could creditably fit the DMH data. The experi...Continue Reading

References

Aug 31, 1990·Science·S M Cohen, L B Ellwein
Jan 1, 1989·Teratogenesis, Carcinogenesis, and Mutagenesis·K T Kitchin, J L Brown
Aug 1, 1987·Environmental Health Perspectives·L ZeiseE A Crouch
Jan 1, 1986·Annual Review of Public Health·S H Moolgavkar

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Citations

Dec 29, 2013·Environmental Science & Technology·Beate I EscherFrederic D L Leusch
May 10, 2000·Bioscience, Biotechnology, and Biochemistry·G WanN Kato
Aug 5, 2008·Toxicology and Applied Pharmacology·Michael Waters, Marcus Jackson
Sep 29, 2015·Critical Reviews in Toxicology·Kenneth T Bogen, Jacqueline M Heilman
Mar 2, 1999·Regulatory Toxicology and Pharmacology : RTP·E J Calabrese, L A Baldwin
Oct 2, 1998·Human & Experimental Toxicology·A TurturroR W Hart
Feb 7, 2017·Oxidative Medicine and Cellular Longevity·Hemantkumar ChavanPartha Krishnamurthy

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