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. 1983 Jul;139(1):55–74.

Chemicals, Cancer and Cancer Biology

Edward A Smuckler
PMCID: PMC1010879  PMID: 6624084

Abstract

Chemicals can cause cancer in humans and animals. Two significant questions are how and how frequently do these neoplasms arise? The first documentation of chemically induced cancer in humans was of the occupationally related “soot wart” in 1775. Since that time various carcinogens have been identified. Some compounds act directly on cell populations, whereas others must be metabolized by a host to produce a “proximate” or “ultimate” carcinogen. Because of the variety in carcinogen structure and the multiplicity of modifications to the cellular macromolecules, a simple explanation for chemical effect is unlikely. Furthermore, true neoplastic growth involves at least two and possibly more steps, some of which are reversible. Evidence suggests that cancer represents an altering of differentiation and that chemical agents may act at the level of DNA or on epigenetic regulatory phenomena. The method for selecting the neoplastic cell from those that are normal is not known. Because we cannot explain the mechanisms for cancer formation or the role of chemicals in the process, prudence is needed in determining the significance of human exposure and in relating this exposure to the risk of neoplastic disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adesnik M., Salditt M., Thomas W., Darnell J. E. Evidence that all messenger RNA molecules (except histone messenger RNA) contain Poly (A) sequences and that the Poly(A) has a nuclear function. J Mol Biol. 1972 Oct 28;71(1):21–30. doi: 10.1016/0022-2836(72)90397-x. [DOI] [PubMed] [Google Scholar]
  2. Agutter P. S., McCaldin B., McArdle H. J. Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins. Biochem J. 1979 Sep 15;182(3):811–819. doi: 10.1042/bj1820811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arcasoy M., Smuckler E. A., Benditt E. P. Acute effects of 3'-methyl-4-dimethylaminoazobenzene intoxication on rat liver. Structural and functional changes in the endoplasmic reticulum and NADPH-related electron transport. Am J Pathol. 1968 Apr;52(4):841–867. [PMC free article] [PubMed] [Google Scholar]
  4. Argyris T. S. Tumor promotion by regenerative epidermal hyperplasia in mouse skin. J Cutan Pathol. 1982 Feb;9(1):1–18. doi: 10.1111/j.1600-0560.1982.tb01036.x. [DOI] [PubMed] [Google Scholar]
  5. Austin G. E., Russo R. J., Moyer G. H. Sequence complexity of nuclear RNA from 2-acetylaminofluorene-induced rat hepatomas and host cirrhotic liver. Carcinogenesis. 1982;3(6):609–613. doi: 10.1093/carcin/3.6.609. [DOI] [PubMed] [Google Scholar]
  6. Blackburn G. R., Schnabel S. J., Danley J. M., Hogue-Angeletti R. A., Sorof S. Principal polypeptide target of carcinogen at the beginning of liver carcinogenesis by three carcinogens. Cancer Res. 1982 Nov;42(11):4664–4672. [PubMed] [Google Scholar]
  7. Boland C. R., Montgomery C. K., Kim Y. S. Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2051–2055. doi: 10.1073/pnas.79.6.2051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Busch H., Reddy R., Rothblum L., Choi Y. C. SnRNAs, SnRNPs, and RNA processing. Annu Rev Biochem. 1982;51:617–654. doi: 10.1146/annurev.bi.51.070182.003153. [DOI] [PubMed] [Google Scholar]
  9. Calabretta B., Robberson D. L., Barrera-Saldaña H. A., Lambrou T. P., Saunders G. F. Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature. 1982 Mar 18;296(5854):219–225. doi: 10.1038/296219a0. [DOI] [PubMed] [Google Scholar]
  10. Churg A., Warnock M. L., Bensch K. G. Malignant mesothelioma arising after direct application of asbestos and fiber glass to the pericardium. Am Rev Respir Dis. 1978 Aug;118(2):419–424. doi: 10.1164/arrd.1978.118.2.419. [DOI] [PubMed] [Google Scholar]
  11. Clawson G. A., Koplitz M., Moody D. E., Smuckler E. A. Effects of thioacetamide treatment on nuclear envelope nucleoside triphosphatase activity and transport of RNA from rat liver nuclei. Cancer Res. 1980 Jan;40(1):75–79. [PubMed] [Google Scholar]
  12. Clawson G. A., Smuckler E. A. Activation energy for RNA transport from isolated rat liver nuclei. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5400–5404. doi: 10.1073/pnas.75.11.5400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Clawson G. A., Smuckler E. A. Increased nucleoside triphosphatase activity of rat liver nuclear matrix following low dose carcinogen intoxication. Biochem Biophys Res Commun. 1982 Oct 15;108(3):1331–1339. doi: 10.1016/0006-291x(82)92146-5. [DOI] [PubMed] [Google Scholar]
  14. Cooper G. M. Cellular transforming genes. Science. 1982 Aug 27;217(4562):801–806. doi: 10.1126/science.6285471. [DOI] [PubMed] [Google Scholar]
  15. Craighead J. E., Abraham J. L., Churg A., Green F. H., Kleinerman J., Pratt P. C., Seemayer T. A., Vallyathan V., Weill H. The pathology of asbestos-associated diseases of the lungs and pleural cavities: diagnostic criteria and proposed grading schema. Report of the Pneumoconiosis Committee of the College of American Pathologists and the National Institute for Occupational Safety and Health. Arch Pathol Lab Med. 1982 Oct 8;106(11):544–596. [PubMed] [Google Scholar]
  16. Doll R., Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981 Jun;66(6):1191–1308. [PubMed] [Google Scholar]
  17. Farber E. Chemical carcinogenesis. N Engl J Med. 1981 Dec 3;305(23):1379–1389. doi: 10.1056/NEJM198112033052304. [DOI] [PubMed] [Google Scholar]
  18. Farber E. Chemical carcinogenesis. N Engl J Med. 1981 Dec 3;305(23):1379–1389. doi: 10.1056/NEJM198112033052304. [DOI] [PubMed] [Google Scholar]
  19. Farber E. Chemical carcinogenesis: a biologic perspective. Am J Pathol. 1982 Feb;106(2):271–296. [PMC free article] [PubMed] [Google Scholar]
  20. Farber E. The sequential analysis of liver cancer induction. Biochim Biophys Acta. 1980 May 6;605(2):149–166. doi: 10.1016/0304-419x(80)90002-5. [DOI] [PubMed] [Google Scholar]
  21. Fialkow P. J. Use of genetic markers to study cellular origin and development of tumors in human females. Adv Cancer Res. 1972;15:191–226. doi: 10.1016/s0065-230x(08)60375-9. [DOI] [PubMed] [Google Scholar]
  22. Fidler I. J., Hart I. R. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982 Sep 10;217(4564):998–1003. doi: 10.1126/science.7112116. [DOI] [PubMed] [Google Scholar]
  23. Forman D., Rowley J. Chromosomes and cancer. Nature. 1982 Dec 2;300(5891):403–404. doi: 10.1038/300403a0. [DOI] [PubMed] [Google Scholar]
  24. Garrett C. T., Katz C., Moore R. E., Pitot H. C. Competitive RNA-DNA hybridization of nuclear and microsomal RNA during diethylnitrosamine hepatocarcinogenesis. Cancer Res. 1973 Jul;33(7):1662–1669. [PubMed] [Google Scholar]
  25. Goodfellow P. N., Andrews P. W. The biology of teratocarcinomas. Nature. 1982 Nov 11;300(5888):107–108. doi: 10.1038/300107a0. [DOI] [PubMed] [Google Scholar]
  26. Goss R. J. Hypertrophy versus hyperplasia. Science. 1966 Sep 30;153(3744):1615–1620. doi: 10.1126/science.153.3744.1615. [DOI] [PubMed] [Google Scholar]
  27. Harris H., Miller O. J., Klein G., Worst P., Tachibana T. Suppression of malignancy by cell fusion. Nature. 1969 Jul 26;223(5204):363–368. doi: 10.1038/223363a0. [DOI] [PubMed] [Google Scholar]
  28. Holliday R., Pugh J. E. DNA modification mechanisms and gene activity during development. Science. 1975 Jan 24;187(4173):226–232. [PubMed] [Google Scholar]
  29. Horm J. W., Asire A. J. Changes in lung cancer incidence and mortality rates among Americans: 1969--78. J Natl Cancer Inst. 1982 Oct;69(4):833–837. [PubMed] [Google Scholar]
  30. Ishikawa K., Kuroda C., Ogata K. Release of ribonucleoprotein particles containing rapidly labeled ribonucleic acid from rat liver nuclei. Effect of adenosine 5'-triphosphate and some properties of the particles. Biochim Biophys Acta. 1969 Apr 22;179(2):316–331. doi: 10.1016/0005-2787(69)90040-9. [DOI] [PubMed] [Google Scholar]
  31. Iversen O. H., Iversen U. M. Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. Br J Cancer. 1982 Jun;45(6):912–920. doi: 10.1038/bjc.1982.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jähner D., Stuhlmann H., Stewart C. L., Harbers K., Löhler J., Simon I., Jaenisch R. De novo methylation and expression of retroviral genomes during mouse embryogenesis. Nature. 1982 Aug 12;298(5875):623–628. doi: 10.1038/298623a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Lewin R. Repeated DNA still in search of a function. Science. 1982 Aug 13;217(4560):621–623. doi: 10.1126/science.6283639. [DOI] [PubMed] [Google Scholar]
  35. Ley T. J., DeSimone J., Anagnou N. P., Keller G. H., Humphries R. K., Turner P. H., Young N. S., Keller P., Nienhuis A. W. 5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia. N Engl J Med. 1982 Dec 9;307(24):1469–1475. doi: 10.1056/NEJM198212093072401. [DOI] [PubMed] [Google Scholar]
  36. Loeb L. A., Kunkel T. A. Fidelity of DNA synthesis. Annu Rev Biochem. 1982;51:429–457. doi: 10.1146/annurev.bi.51.070182.002241. [DOI] [PubMed] [Google Scholar]
  37. Logan J., Cairns J. The secrets of cancer. Nature. 1982 Nov 11;300(5888):104–105. doi: 10.1038/300104a0. [DOI] [PubMed] [Google Scholar]
  38. MAGEE P. N., FARBER E. Toxic liver injury and carcinogenesis. Methylation of rat-liver nucleic acids by dimethylnitrosamine in vivo. Biochem J. 1962 Apr;83:114–124. doi: 10.1042/bj0830114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. MAGEE P. N., HULTIN T. Toxic liver injury and carcinogenesis. Methylation of proteins of rat-liver slices by dimethylnitrosamine in vitro. Biochem J. 1962 Apr;83:106–114. doi: 10.1042/bj0830106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Martin G. R. Teratocarcinomas and mammalian embryogenesis. Science. 1980 Aug 15;209(4458):768–776. doi: 10.1126/science.6250214. [DOI] [PubMed] [Google Scholar]
  41. Marx J. L. Genes that control development. Science. 1981 Sep 25;213(4515):1485–1488. doi: 10.1126/science.6792705. [DOI] [PubMed] [Google Scholar]
  42. Maskens A. P., Dujardin-Loits R. M. Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa. Cancer. 1981 Jan 1;47(1):81–89. doi: 10.1002/1097-0142(19810101)47:1<81::aid-cncr2820470115>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  43. McLean A. E., Magee P. N. Increased renal carcinogenesis by dimethyl nitrosamine in protein deficient rats. Br J Exp Pathol. 1970 Dec;51(6):587–590. [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Mintz B., Cronmiller C. Normal blood cells of anemic genotype in teratocarcinoma-derived mosaic mice. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6247–6251. doi: 10.1073/pnas.75.12.6247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Mintz B., Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585–3589. doi: 10.1073/pnas.72.9.3585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  48. Ozanne B., Wheeler T., Zack J., Smith G., Dale B. Transforming gene of a human leukaemia cell is unrelated to the expressed tumour virus related gene of the cell. Nature. 1982 Oct 21;299(5885):744–747. doi: 10.1038/299744a0. [DOI] [PubMed] [Google Scholar]
  49. Peraino C., Fry R. J., Staffeldt E., Christopher J. P. Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Cancer Res. 1975 Oct;35(10):2884–2890. [PubMed] [Google Scholar]
  50. Pierce G. B., Pantazis C. G., Caldwell J. E., Wells R. S. Specificity of the control of tumor formation by the blastocyst. Cancer Res. 1982 Mar;42(3):1082–1087. [PubMed] [Google Scholar]
  51. Potter S. S. DNA sequence of a foldback transposable element in Drosophila. Nature. 1982 May 20;297(5863):201–204. doi: 10.1038/297201a0. [DOI] [PubMed] [Google Scholar]
  52. Pulciani S., Santos E., Lauver A. V., Long L. K., Robbins K. C., Barbacid M. Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells. Proc Natl Acad Sci U S A. 1982 May;79(9):2845–2849. doi: 10.1073/pnas.79.9.2845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Razin A., Riggs A. D. DNA methylation and gene function. Science. 1980 Nov 7;210(4470):604–610. doi: 10.1126/science.6254144. [DOI] [PubMed] [Google Scholar]
  54. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  55. Riggs A. D. X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet. 1975;14(1):9–25. doi: 10.1159/000130315. [DOI] [PubMed] [Google Scholar]
  56. Salditt-Georgieff M., Darnell J. E., Jr Further evidence that the majority of primary nuclear RNA transcripts in mammalian cells do not contribute to mRNA. Mol Cell Biol. 1982 Jun;2(6):701–707. doi: 10.1128/mcb.2.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Santella R. M., Grunberger D., Nordheim A., Rich A. N-2-Acetylaminofluorene modification of poly(dG-m5dC) . poly(dG-m5dC) induces the Z-DNA conformation. Biochem Biophys Res Commun. 1982 Jun 30;106(4):1226–1232. doi: 10.1016/0006-291x(82)91243-8. [DOI] [PubMed] [Google Scholar]
  58. Saunders F. C., Barker E. A., Smuckler E. A. Selective inhibition of nucleoplasmic rat liver DNA-dependent RNA polymerase by aflatoxin B 1 . Cancer Res. 1972 Nov;32(11):2487–2494. [PubMed] [Google Scholar]
  59. Schmid C. W., Jelinek W. R. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. doi: 10.1126/science.6281889. [DOI] [PubMed] [Google Scholar]
  60. Schumm D. E., Hanausek-Walaszek M., Yannarell A., Webb T. E. Changes in nuclear RNA transport incident to carcinogenesis. Eur J Cancer. 1977 Feb;13(2):139–147. doi: 10.1016/0014-2964(77)90192-x. [DOI] [PubMed] [Google Scholar]
  61. Sell S., Leffert H. L. An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology. 1982 Jan-Feb;2(1):77–86. doi: 10.1002/hep.1840020113. [DOI] [PubMed] [Google Scholar]
  62. Shearer R. W., McCarthy B. J. Characterization of RNA molecules restricted to the nucleus in mouse L-cells. J Cell Physiol. 1970 Feb;75(1):97–106. doi: 10.1002/jcp.1040750112. [DOI] [PubMed] [Google Scholar]
  63. Shearer R. W., Smuckler E. A. A search for gene derepression in RNA of primary rat hepatomas. Cancer Res. 1971 Dec;31(12):2104–2109. [PubMed] [Google Scholar]
  64. Shearer R. W., Smuckler E. A. Altered regulation of the transport of RNA from nucleus to cytoplasm in rat hepatoma cells. Cancer Res. 1972 Feb;32(2):339–342. [PubMed] [Google Scholar]
  65. Shearer R. W. Specificity of chemical modification of ribonucleic acid transport by liver carcinogens in the rat. Biochemistry. 1974 Apr 9;13(8):1764–1767. doi: 10.1021/bi00705a032. [DOI] [PubMed] [Google Scholar]
  66. Shimkin M. B., Triolo V. A. History of chemical carcinogenesis: some prospective remarks. Prog Exp Tumor Res. 1969;11:1–20. doi: 10.1159/000391385. [DOI] [PubMed] [Google Scholar]
  67. Skinner D. G., Richie J. P., Cooper P. H., Waisman J., Kaufman J. J. The clinical significance of carcinoma in situ of the bladder and its association with overt carcinoma. J Urol. 1974 Jul;112(1):68–71. doi: 10.1016/s0022-5347(17)59645-7. [DOI] [PubMed] [Google Scholar]
  68. Smuckler E. A., Koplitz M., Sell S. alpha-Fetoprotein in toxic liver injury. Cancer Res. 1976 Dec;36(12):4558–4561. [PubMed] [Google Scholar]
  69. Smuckler E. A., Koplitz M. Thioacetamide-induced alterations in nuclear RNA transport. Cancer Res. 1974 Apr;34(4):827–838. [PubMed] [Google Scholar]
  70. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  71. Talmadge J. E., Fidler I. J. Cancer metastasis is selective or random depending on the parent tumour population. Nature. 1982 Jun 17;297(5867):593–594. doi: 10.1038/297593a0. [DOI] [PubMed] [Google Scholar]
  72. Topal M. D., Baker M. S. DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2211–2215. doi: 10.1073/pnas.79.7.2211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Wheeler J. E., Enterline H. T. Lobular carcinoma of the breast in situ and infiltrating. Pathol Annu. 1976;11:161–188. [PubMed] [Google Scholar]
  74. Wilson J. S., Holland L. M. The effect of application frequency on epidermal carcinogenesis assays. Toxicology. 1982;24(1):45–53. doi: 10.1016/0300-483x(82)90061-0. [DOI] [PubMed] [Google Scholar]
  75. Woodruff M. F., Ansell J. D., Forbes G. M., Gordon J. C., Burton D. I., Micklem H. S. Clonal interaction in tumours. Nature. 1982 Oct 28;299(5886):822–824. doi: 10.1038/299822a0. [DOI] [PubMed] [Google Scholar]
  76. Yamakawa M., Furuichi Y., Shatkin A. J. Priming of reovirus transcription by GppppG and formation of CpG(5')GpC. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6142–6146. doi: 10.1073/pnas.79.20.6142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Zeevi M., Nevins J. R., Darnell J. E., Jr Newly formed mRNA lacking polyadenylic acid enters the cytoplasm and the polyribosomes but has a shorter half-life in the absence of polyadenylic acid. Mol Cell Biol. 1982 May;2(5):517–525. doi: 10.1128/mcb.2.5.517. [DOI] [PMC free article] [PubMed] [Google Scholar]

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