US EPA

3045581 

Book/Book Chapter 

Carcinogenesis: Mechanisms and manifestations 

Malarkey, DE; Hoenerhoff,M; Maronpot, RR 

2013 

Academic Press 

Waltham, MA 

Haschek and Rousseaux's handbook of toxicologic pathology 

I 

107–146 

English 

10.1016/B978-0-12-415759-0.00005-4 

http://www.sciencedirect.com/science/article/pii/B9780124157590000054
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is a chapter of 3042124 Haschek and Rousseaux's handbook of toxicologic pathology

Identifying potential human carcinogens in rodent bioassays has been a major focus of the field of toxicologic pathology for decades. Animal and human cancers are fundamentally similar and frequently share morphological, biological, and molecular biological features. Cancer develops as a function of age, environment, diet, and genetic makeup. To date, the 2-year rodent carcinogenicity study appears to be the single best system for identifying carcinogenic potential. Not only has the 2-year rodent carcinogenicity test been sufficiently sensitive in identifying known human carcinogens, it has also identified carcinogens such as aflatoxin, 4-aminobiphenyl, bis(chloromethyl) ether, diethylstilbestrol (DES), melphalan, mustard gas, and vinyl chloride prior to discovery of their carcinogenicity in humans. The 2-year bioassay is costly and time-intensive, and may be misidentifying some agents as human carcinogens. With our greater understanding of the carcinogenic processes and the advent of new molecular technologies, such as gene and protein expression arrays, massive amounts of biological information are being generated and serve as the basis for our better understanding of the carcinogenic processes and molecular mechanisms of the risks for cancer development in man and animals. Promising short- and medium-term assays to identify relevant predictive profiles of carcinogenicity in humans are being proposed. We are also on the brink of major breakthroughs concerning the early detection, prevention, and treatment of cancer. This chapter reviews the fundamental mechanisms and current understanding of the biological and molecular basis of chemical carcinogenesis as a framework for interpreting bioassay results and mechanistic data. 

3rd 

Haschek, W; Rousseaux, C; Wallig, M 

Practice of Toxicologic Pathology 

9780124157590