Relevance of Animal Carcinogenesis Findings to Human Cancer Predictions and Prevention

Abstract

Use of laboratory animals to identify carcinogenic potential of chemicals, mixtures, and other agents has a modern history of greater than 40 years from which much useful scientific and public health information can be derived. While laboratory animals differ from humans in some respects that may affect responses to hazardous exposures, use of such models is based on experimental evidence indicating that there are more genetic, genomic, physiological, biochemical, and metabolic similarities than differences among mammalian species. Issues of concordance of responses between rodent species and between rodents and humans as well as repeatability and site-specificity are important considerations in evaluating laboratory animal carcinogenicity results. Variables in experimental design such as animal strain, diet, route of exposure, and study, duration as well as single-site versus multisite carcinogenic responses all influence interpretation and intelligent use of study data. Similarities and differences in site-specific laboratory animal and corresponding human cancers should also be considered in study evaluation. Recent attempts to explore genetically engineered mice and to humanize the mouse for more relevant identification of carcinogen hazard identification have yielded mixed results. In the end we are confronted by the realization that virtually all animal cancer models are useful but imperfect surrogates for humans. Assuming the percentage of chemicals currently in commerce that are estimated to be potent animal or human carcinogens is quite low, the task of identifying agents with significant carcinogenic potential is daunting and important. The biological conundrum of scientific debate regarding the relevance of carcinogenicity studies in laboratory animals is likely to continue. Nonetheless public health considerations must take precedence when deciding human safety issues.

Scientific Opinion on acrylamide in food

“…The CONTAM Panel considered that even though the Harderian gland is not present in humans, this rodent organ represents a sensitive endpoint for detecting compounds that are both genotoxic and carcinogenic (Cohen, 2004;Maronpot et al, 2004;Edler et al, 2014). Harderian gland tumours and tumours in other rodent organs including the lung in mice, the brain in rats, and the mammary gland and forestomach in both species are prone to tumour formation upon exposure to epoxides or epoxideforming carcinogens (Melnick, 2002), such as AA.…”

Proteomic profiling of animal models mimicking skeletal muscle disorders

“…Over the last few decades, both naturally occurring and genetically engineered animal models of human diseases have been employed for evaluating new therapeutic options and for elucidating pathological pathways [1][2][3][4][5][6][7][8][9]. In conjunction with findings from clinical investigations, biological studies of animal models can be extremely helpful for the initial evaluation of alternative treatment strategies [10][11][12]. Genetic manipulations via transgenic or gene knockout technology can provide crucial information prior to the development of drug or gene therapy approaches to counter-act symptoms in human disorders [13,14].…”

The carcinogenic effects of aspartame: The urgent need for regulatory re‐evaluation

“…First we must consider that, for >40 years, there has been general agreement amongst experts in chemical carcinogenesis that substances that cause significantly increased incidence of cancers in experimental animals, in wellconducted long-term bioassays, pose a presumptive and predictive carcinogenic risk to humans, even in the absence of conclusive epidemiological data [Tomatis, 1979;Maltoni et al, 1999;Maronpot et al, 2004;Cogliano, 2006;Huff, 2010].…”