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Toxicologic Pathology
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Journal Article

Pathologist's Responsibility in the Diagnosis of Oncogenesis

Michael J. Iatropoulos

Department of Experimental Pathology, W.G. Malcolm Toxicology Laboratories, American Cyanamid Company, Pearl River, New York 10965, U.S.A.

In recent years with all sophisticated incoming data, it has become obvious that "cancer" is indeed a cellular disease. This level of biological organization is extremely pivotal, because it is at this level that the interactive control mechanisms have failed, rendering excessive proliferation and uncoordinated growth, which persists after cessation of the stimuli which evoked it. Although we are extremely interested in identifying and describing the stimuli (etiology), presently as toxicologic pathologists, we are called upon in rendering a diagnosis as to whether given findings are "cancer", and by extension whether an administered substance has caused these findings in laboratory animal species. For some time now the etiology has been confused with the diagnosis and the identification of the causative stimuli with the manifested effects. Although we don't know yet the entire story about the etiology of the oncogenic process we can say that we know a lot about its manifestations and therefore we are capable of making the diagnosis. By virtue of our training, we are capable of identifying, classifying and describing all oncogenic manifestations, no matter whether they are in mice or men. In the course of this pursuit we need some order. Oncogenesis is a multistep, multistage process. We must therefore have a design capable of describing and differentiating initiation, potentiation, promotion, modification, and autonomy in our laboratory animal studies. We must also address the status of the biological resistance of the animal organism through pertinent comparative correlations. Furthermore, since "cancer" is a disease, and a syndrome, we must not limit ourselves in studying only the incidence of a single manifestation in an animal, especially if we intend to use it in extrapolation, but the entire multiplicity of manifestations. In biology, in order to effectively extrapolate, we need appropriate changes in the orders of magnitude. The new chemical entity should be compared structurally to the known human and rodent oncogenic substances. The interspecies differences in toxicokinetics and metabolism compared and the type and location of target cell, as well as, the extent of genetic distortions should be established. By implementing all these it is possible not only to render an accurate diagnosis but also estimate the human "cancer" risk.

  • 1. Meissner WA, Diamandopoulos GT (1977): Neoplasia. In Pathology. WAD Anderson and JM Kissane (editors). Vol I. C. V. Mosby Company, Saint Louis, pp. 640–691.
  • 2. Cairns J (1981): The Origin of Human Cancers. Nature (London) 289:353–357.[CrossRef][Medline] [Order article via Infotrieve]
  • 3. Becker FF (1979): Evolution, Chemical Carcinogenesis and Mortality. In "Carcinogenes: Identification and Mechanisms of Action". A. C. Griffin and C. R. Shaw (editors), Raven Press, New York, pp 5–17.
  • 4. Cooper GM (1982): Cellular Transforming Genes. Science 217: 801–806.[Abstract/Free Full Text]
  • 5. Calabrese EJ (1983): DNA Repair: Interspecies Differences. In "Principles of Animal Extropolation." E. J. Calabrese (editor), John Wiley & Sons, New York, pp. 467–479.
  • 6. Goss RJ (1966): Hypertrophy Versus Hyperplasia. Science 153: 1615–1620.[Abstract/Free Full Text]
  • 7. Anderson MW, Hoel DG, Kaplan NL (1980): A General Scheme for the Incorporation of Pharmacokinetics in Low-dose Risk Estimation for Chemical Carcinogenesis: Example–-Vinyl Chloride. Toxicol Appl Pharmacol 55: 154–161.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 8. Russo J, Russo IH (1983): Basis of Cellular Autonomy in the Susceptibility to Carcinogenesis. Toxicologic Path. (in press).
  • 9. Hill BT (1982): Biochemical and Cell Kinetic Aspects of Drug Resistance. In "Drug and Hormone Resistance in Neóplasia." N. Bruchovsky and J. H. Goldie (editors), CRC Press, Boca Raton, Florida, pp. 21–53.
  • 10. Pitot HC (1977): Carcinogenesis and Aging–-Two Related Phenomena? Am J of Pathol 87: 444–472.
  • 11. Tomatis L, Partensky C, Montesano R (1973): The Predictive Value of Mouse Liver Tumour Induction in Carcinogenicity Testing. Int J Cancer 12: 1–20.[Web of Science][Medline] [Order article via Infotrieve]
  • 12. De La Iglesia FA, Barsoum N, Gough A, Mitchell L, Martin RA, DiFonzo C, McGuire EJ (1981): Carcinogenesis Bioassay of Prazepam in Rats and Mice. Toxicol Appl Pharmacol 57: 34–54.
  • 13. Nelson CJ, Baetcke KP, Frith CH, Kodell RL, Schief-ferstein G (1982): The Influence of Sex, Dose, Time, and Cross on Neoplasia in Mice Given Benzidine Dihydrochloride. Toxicol Appl Pharmacol 64: 171–186.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 14. Goodman DG, Ward JM, Squire RA, Chu KC, Linhart MS (1979): Neoplastic and Non-neoplastic Lesions in Aging F344 Rats. Toxicol Appl Pharmacol 40: 237–248.
  • 15. Goodman DG, Ward JW, Squire RA, Paxton MB, Reichardt WD, Chu KC, Linhart MS (1980): Neoplastic and Non-Neoplastic Lesions in Aging Osborne-Mendel Rats. Toxicol Appl Pharmacol 55: 433–447.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 16. Leslie GB, Noakes DN, Pollitt FD, Roe FJC, Walker TF (1981): A Two-Year Study with Cimetidine in the Rat: Assessment for Chronic Toxicity and Carcinogenicity. Toxicol Appl Pharmacol 61: 119–137.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 17. Turusov VS (1973): Pathology of Tumours in Laboratory Animals. Vol. I, Part 1, Tumours of the Rat. Int Agency Res Cancer, (IARC Sci. Publ. 5) Lyon, France.
  • 18. Turusov VS (1976): Pathology of Tumours in Laboratory Animals. Vol. I, Part 2, Tumours of the Rat. Int Agency Res Cancer, (IARC Sci. Publ. 6) Lyon, France.
  • 19. Turusov VS (1979): Pathology of Tumours in Laboratory Animals. Vol. II, Tumours of the Mouse. Int Agency Res Cancer, (IARC Sci. Publ. 23) Lyon, France.
  • 20. Higginson J (1977): The Role of the Pathologist in Environmental Medicine and Public Health. Am J Pathol 86: 460–484.[Abstract]
  • 21. Leuschner F, Neumann W, Hempel R (1980): Toxicology of Antipsychotic Agents. In Psychotropic Agents, Hoffmeister F. and G. Stille (editors), Springer Verlag, Berlin.
  • 22. Welsch CW, Nagasawa H (1977): Prolactin and Murine Mammary Tumorigenesis, Cancer Res. 27: 951–963.
  • 23. Short RV, Drife JO (1977): The Aetiology of Mammary Cancer in Man and Animals. Symp R Soc London, No. 41 p. 211–230.

Toxicologic Pathology, Vol. 11, No. 2, 132-142 (1983)
DOI: 10.1177/019262338301100205


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This Article
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*Cancer
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