Abstract
Some highlights in the development of our knowledge about carcinogens as etiological agents for cancer are reviewed briefly. Advances during the past 20 years relating to metabolic activation with the genesis of reactive metabolites, molecular targets and their interactions with activated carcinogens, oncogenes as molecular targets and the dependence on cell proliferation, all relating to the initiation process, are reviewed. Critical to initiation is the new phenotype in the initiated cell, known only in one instance, the rat liver, in which the characteristic change is one of resistance to many xenobiotic influences. The need for clonal expansion of initiated cells as essential for carcinogenic effects is discussed. Differential inhibition has been shown as a dominant mechanistic pattern in the liver. In other systems, the manner in which clonal expansion is achieved is not evident. The need for studies of the processes involved in carcinogenesis, as well as the agents, is emphasized, in view of the continuing validity of the cell concept as the key to integrating the increasingly large volume of data from the molecular with the biological.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barbacid M. Oncogenes and human cancer: cause or consequence? Carcinogenesis. 1986 Jul;7(7):1037–1042. doi: 10.1093/carcin/7.7.1037. [DOI] [PubMed] [Google Scholar]
- Borek C., Sachs L. In vitro cell transformation by x-irradiation. Nature. 1966 Apr 16;210(5033):276–278. doi: 10.1038/210276a0. [DOI] [PubMed] [Google Scholar]
- Cayama E., Tsuda H., Sarma D. S., Farber E. Initiation of chemical carcinogenesis requires cell proliferation. Nature. 1978 Sep 7;275(5675):60–62. doi: 10.1038/275060a0. [DOI] [PubMed] [Google Scholar]
- Conney A. H. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture. Cancer Res. 1982 Dec;42(12):4875–4917. [PubMed] [Google Scholar]
- Denhardt D. T., Edwards D. R., Parfett C. L. Gene expression during the mammalian cell cycle. Biochim Biophys Acta. 1986 Oct 28;865(2):83–125. doi: 10.1016/0304-419x(86)90024-7. [DOI] [PubMed] [Google Scholar]
- Farber E. Carcinogenesis--cellular evolution as a unifying thread: Presidential address. Cancer Res. 1973 Nov;33(11):2537–2550. [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]
- Farber E. Chemical carcinogenesis: a biologic perspective. Am J Pathol. 1982 Feb;106(2):271–296. [PMC free article] [PubMed] [Google Scholar]
- Farber E., Sarma D. S. Hepatocarcinogenesis: a dynamic cellular perspective. Lab Invest. 1987 Jan;56(1):4–22. [PubMed] [Google Scholar]
- Farber E. The biochemistry of preneoplastic liver: a common metabolic pattern in hepatocyte nodules. Can J Biochem Cell Biol. 1984 Jun;62(6):486–494. doi: 10.1139/o84-066. [DOI] [PubMed] [Google Scholar]
- Fox T. R., Watanabe P. G. Detection of a cellular oncogene in spontaneous liver tumors of B6C3F1 mice. Science. 1985 May 3;228(4699):596–597. doi: 10.1126/science.3983645. [DOI] [PubMed] [Google Scholar]
- Hennings H., Yuspa S. H. Two-stage tumor promotion in mouse skin: an alternative interpretation. J Natl Cancer Inst. 1985 Apr;74(4):735–740. [PubMed] [Google Scholar]
- Kaczmarek L. Protooncogene expression during the cell cycle. Lab Invest. 1986 Apr;54(4):365–376. [PubMed] [Google Scholar]
- Kakunaga T. Requirement for cell replication in the fixation and expression of the transformed state in mouse cells treated with 4-nitroquinoline-1-oxide. Int J Cancer. 1974 Dec 15;14(6):736–742. doi: 10.1002/ijc.2910140607. [DOI] [PubMed] [Google Scholar]
- Leonard T. B., Dent J. G., Graichen M. E., Lyght O., Popp J. A. Comparison of hepatic carcinogen initiation-promotion systems. Carcinogenesis. 1982;3(8):851–856. doi: 10.1093/carcin/3.8.851. [DOI] [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]
- Reynolds S. H., Stowers S. J., Maronpot R. R., Anderson M. W., Aaronson S. A. Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse. Proc Natl Acad Sci U S A. 1986 Jan;83(1):33–37. doi: 10.1073/pnas.83.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roomi M. W., Ho R. K., Sarma D. S., Farber E. A common biochemical pattern in preneoplastic hepatocyte nodules generated in four different models in the rat. Cancer Res. 1985 Feb;45(2):564–571. [PubMed] [Google Scholar]
- Tatematsu M., Murasaki G., Nakanishi K., Miyata Y., Shinohara Y., Ito N. Sequential quantitative studies on hyperplastic nodules in the liver of rats treated with carcinogenic chemicals. Gan. 1979 Feb;70(1):125–130. [PubMed] [Google Scholar]
- Tsuda H., Farber E. Resistant hepatocytes as early changes in liver induced by polycyclic aromatic hydrocarbons. Int J Cancer. 1980 Jan 15;25(1):137–139. doi: 10.1002/ijc.2910250118. [DOI] [PubMed] [Google Scholar]
- Tsuda H., Lee G., Farber E. Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens. Cancer Res. 1980 Apr;40(4):1157–1164. [PubMed] [Google Scholar]
- Wiseman R. W., Stowers S. J., Miller E. C., Anderson M. W., Miller J. A. Activating mutations of the c-Ha-ras protooncogene in chemically induced hepatomas of the male B6C3 F1 mouse. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5825–5829. doi: 10.1073/pnas.83.16.5825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Heijden C. A., Dormans J. A. Short-term induction of neoplastic nodules in the rat liver. II. Study of their development and the effects of withdrawal of 2-acetylaminofluorene. Carcinogenesis. 1981;2(2):147–156. doi: 10.1093/carcin/2.2.147. [DOI] [PubMed] [Google Scholar]
- van der Heijden C. A., Dormans J. A., van Nesselrooij J. H. Short term induction of preneoplastic nodules in the rat liver. I. The role of 2-AAF as selecting agent. Eur J Cancer. 1980 Nov;16(11):1389–1398. doi: 10.1016/0014-2964(80)90047-x. [DOI] [PubMed] [Google Scholar]
