Abstract
The many anatomical, physiological, and biochemical differences among various mammalian species make it difficult to extrapolate carcinogenic potency data from animals to humans. The process is further complicated by the multistep origin of most malignant tumors in animals and humans due to the interaction of target cells with both endogenous and exogenous factors. Species differences in these aspects of carcinogenesis must also be considered when attempting to evaluate the carcinogenic risks of chemicals to humans. Cancer development in animals involves at least three distinct stages: initiation, promotion, and progression. Intra- and interspecies differences in susceptibility to carcinogenesis may be related to any one or a combination of these stages. Variation in species susceptibility to tumor initiation may result from differences in the abilities of various species to metabolize a potential carcinogen to an ultimate carcinogenic form and/or to detoxify the carcinogen. Most comparative studies among species have only revealed subtle differences in metabolism. DNA adducts from several activated carcinogens have been found to be the same in a number of tissues from various species, including humans. Capacity for DNA repair is apparently a critical factor in the initiation of carcinogenesis in target cells of different species but is less critical among mice that differ in susceptibility to two-stage carcinogenesis of the skin and liver. Susceptibility variations among stocks and strains to such carcinogenesis appear to be related to alterations in tumor promotion. Additional comparative studies are critically needed on all aspects of carcinogenesis to permit effective extrapolation of carcinogenic potency data from animals to humans.
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Selected References
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- Adamson R. H., Cooper R. W., O'Gara R. W. Carcinogen-induced tumors in primitive primates. J Natl Cancer Inst. 1970 Sep;45(3):555–559. [PubMed] [Google Scholar]
- Adamson R. H., Sieber S. M. Chemical carcinogenesis studies in nonhuman primates. Basic Life Sci. 1983;24:129–156. doi: 10.1007/978-1-4684-4400-1_7. [DOI] [PubMed] [Google Scholar]
- Ashurst S. W., Cohen G. M., Nesnow S., DiGiovanni J., Slaga T. J. Formation of benzo(a)pyrene/DNA adducts and their relationship to tumor initiation in mouse epidermis. Cancer Res. 1983 Mar;43(3):1024–1029. [PubMed] [Google Scholar]
- BROOKES P., LAWLEY P. D. EVIDENCE FOR THE BINDING OF POLYNUCLEAR AROMATIC HYDROCARBONS TO THE NUCLEIC ACIDS OF MOUSE SKIN: RELATION BETWEEN CARCINOGENIC POWER OF HYDROCARBONS AND THEIR BINDING TO DEOXYRIBONUCLEIC ACID. Nature. 1964 May 23;202:781–784. doi: 10.1038/202781a0. [DOI] [PubMed] [Google Scholar]
- Booth S. C., Bösenberg H., Garner R. C., Hertzog P. J., Norpoth K. The activation of aflatoxin B1 in liver slices and in bacterial mutagenicity assays using livers from different species including man. Carcinogenesis. 1981;2(10):1063–1068. doi: 10.1093/carcin/2.10.1063. [DOI] [PubMed] [Google Scholar]
- Croy R. G., Essigmann J. M., Wogan G. N. Aflatoxin B1: correlations of patterns of metabolism and DNA modification with biological effects. Basic Life Sci. 1983;24:49–62. doi: 10.1007/978-1-4684-4400-1_3. [DOI] [PubMed] [Google Scholar]
- DiGiovanni J., Prichett W. P., Decina P. C., Diamond L. DBA/2 mice are as sensitive as SENCAR mice to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Carcinogenesis. 1984 Nov;5(11):1493–1498. doi: 10.1093/carcin/5.11.1493. [DOI] [PubMed] [Google Scholar]
- DiGiovanni J., Slaga T. J., Boutwell R. K. Comparison of the tumor-initiating activity of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene in female SENCAR and CS-1 mice. Carcinogenesis. 1980 May;1(5):381–389. doi: 10.1093/carcin/1.5.381. [DOI] [PubMed] [Google Scholar]
- Diwan B. A., Rice J. M., Ohshima M., Ward J. M. Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV- and DBA/2NCr mice. Carcinogenesis. 1986 Feb;7(2):215–220. doi: 10.1093/carcin/7.2.215. [DOI] [PubMed] [Google Scholar]
- Farber E. Cellular biochemistry of the stepwise development of cancer with chemicals: G. H. A. Clowes memorial lecture. Cancer Res. 1984 Dec;44(12 Pt 1):5463–5474. [PubMed] [Google Scholar]
- Friedberg E. C., Bonura T., Love J. D., McMillan S., Radany E. H., Schultz R. A. The repair of DNA damage: recent developments and new insights. J Supramol Struct Cell Biochem. 1981;16(1):91–103. doi: 10.1002/jsscb.1981.380160109. [DOI] [PubMed] [Google Scholar]
- Hanawalt P. C., Cooper P. K., Ganesan A. K., Smith C. A. DNA repair in bacteria and mammalian cells. Annu Rev Biochem. 1979;48:783–836. doi: 10.1146/annurev.bi.48.070179.004031. [DOI] [PubMed] [Google Scholar]
- Harris C. C., Autrup H., Connor R., Barrett L. A., McDowell E. M., Trump B. F. Interindividual variation in binding of benzo[a]pyrene to DNA in cultured human bronchi. Science. 1976 Dec 3;194(4269):1067–1069. doi: 10.1126/science.982061. [DOI] [PubMed] [Google Scholar]
- Juchau M. R. Species and organ differences in the biotransformation of chemical carcinogens. Basic Life Sci. 1983;24:273–281. doi: 10.1007/978-1-4684-4400-1_14. [DOI] [PubMed] [Google Scholar]
- Kleihues P., Hodgson R. M., Veit C., Schweinsberg F., Wiessler M. DNA modification and repair in vivo: towards a biochemical basis of organ-specific carcinogenesis by methylating agents. Basic Life Sci. 1983;24:509–529. doi: 10.1007/978-1-4684-4400-1_27. [DOI] [PubMed] [Google Scholar]
- MILLER E. C., MILLER J. A., ENOMOTO M. THE COMPARATIVE CARCINOGENICITIES OF 2-ACETYLAMINOFLUORENE AND ITS N-HYDROXY METABOLITE IN MICE, HAMSTERS, AND GUINEA PIGS. Cancer Res. 1964 Dec;24:2018–2031. [PubMed] [Google Scholar]
- Miller E. C. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. Cancer Res. 1978 Jun;38(6):1479–1496. [PubMed] [Google Scholar]
- Mirvish S. S., Wallcave L., Eagen M., Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science. 1972 Jul 7;177(4043):65–68. doi: 10.1126/science.177.4043.65. [DOI] [PubMed] [Google Scholar]
- Montesano R. Alkylation of DNA and tissue specificity in nitrosamine carcinogenesis. J Supramol Struct Cell Biochem. 1981;17(3):259–273. doi: 10.1002/jsscb.380170307. [DOI] [PubMed] [Google Scholar]
- Montesano R., Bresil H., Planche-Martel G., Pegg A. E., Margison G. Modification of DNA repair processes induced by nitrosamines. Basic Life Sci. 1983;24:531–543. doi: 10.1007/978-1-4684-4400-1_28. [DOI] [PubMed] [Google Scholar]
- Pegg A. E. Repair of alkylated DNA by cell extracts from various organs and species. Basic Life Sci. 1983;24:545–563. doi: 10.1007/978-1-4684-4400-1_29. [DOI] [PubMed] [Google Scholar]
- Phillips D. H., Grover P. L., Sims P. The covalent binding of polycyclic hydrocarbons to DNA in the skin of mice of different strains. Int J Cancer. 1978 Oct 15;22(4):487–494. doi: 10.1002/ijc.2910220419. [DOI] [PubMed] [Google Scholar]
- Reiners J. J., Jr, Nesnow S., Slaga T. J. Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion. Carcinogenesis. 1984 Mar;5(3):301–307. doi: 10.1093/carcin/5.3.301. [DOI] [PubMed] [Google Scholar]
- Rice J. M., Frith C. H. The nature of organ specificity in chemical carcinogenesis. Basic Life Sci. 1983;24:1–22. doi: 10.1007/978-1-4684-4400-1_1. [DOI] [PubMed] [Google Scholar]
- Rice J. M., Perantoni A. Organ specificity and interspecies differences in carcinogenesis by metabolism-independent alkylating agents. Basic Life Sci. 1983;24:77–105. doi: 10.1007/978-1-4684-4400-1_5. [DOI] [PubMed] [Google Scholar]
- Selkirk J. K., MacLeod M. C., Mansfield B. K., Nikbakht P. A., Dearstone K. C. Species heterogeneity in the metabolic processing of benzo[a]pyrene. Basic Life Sci. 1983;24:283–294. doi: 10.1007/978-1-4684-4400-1_15. [DOI] [PubMed] [Google Scholar]
- Setlow R. B. Repair deficient human disorders and cancer. Nature. 1978 Feb 23;271(5647):713–717. doi: 10.1038/271713a0. [DOI] [PubMed] [Google Scholar]
- Sisskin E. E., Gray T., Barrett J. C. Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with 12-O-tetra-decanoylphorbol-13-acetate. Carcinogenesis. 1982;3(4):403–407. doi: 10.1093/carcin/3.4.403. [DOI] [PubMed] [Google Scholar]
- Slaga T. J., Buty S. G., Thompson S., Bracken W. M., Viaje A. A kinetic study on the in vitro covalent binding of polycyclic hydrocarbons to nucleic acids using epidermal homogenates as the activating system. Cancer Res. 1977 Sep;37(9):3126–3131. [PubMed] [Google Scholar]
- Slaga T. J., Fischer S. M. Strain differences and solvent effects in mouse skin carcinogenesis experiments using carcinogens, tumor initiators and promoters. Prog Exp Tumor Res. 1983;26:85–109. doi: 10.1159/000407254. [DOI] [PubMed] [Google Scholar]
- Slaga T. J., Fischer S. M., Weeks C. E., Klein-Szanto A. J., Reiners J. Studies on the mechanisms involved in multistage carcinogenesis in mouse skin. J Cell Biochem. 1982;18(1):99–119. doi: 10.1002/jcb.1982.240180109. [DOI] [PubMed] [Google Scholar]
- Takeishi K., Okuno-Kaneda S., Seno T. Mutagenic activation of 2-acetylaminofluorene by guinea-pig liver homogenates: essential involvement of cytochrome P-450 mixed-function oxidases. Mutat Res. 1979 Oct;62(3):425–437. doi: 10.1016/0027-5107(79)90038-1. [DOI] [PubMed] [Google Scholar]
- Weinstein I. B. Current concepts and controversies in chemical carcinogenesis. J Supramol Struct Cell Biochem. 1981;17(2):99–120. doi: 10.1002/jsscb.380170202. [DOI] [PubMed] [Google Scholar]
