Carcinogenic and Mutagenic Effects of PCBs

Conference paper
Part of the Environmental Toxin Series book series (TOXIN SERIES, volume 1)


Polychlorinated biphenyls (PCBs) have been the subject of extensive experimental and epidemiological investigation as potential carcinogens. The available evidence indicates that PCBs are weak genotoxicants and initiators of carcinogenesis. However, at levels above a threshold, PCBs are potent promoters of hepatic carcinogenesis in laboratory rodents. While PCBs are able to enhance the biological generation of genotoxic metabolites of many carcinogens in vitro, they usually have the opposite effect in vivo and are capable of preventing carcinogenicity of various organ-specific carcinogens. Epidemiological studies on human and animal populations exposed to PCBs in the environment have so far not revealed clear evidence for carcinogenicity of PCBs under natural exposure circumstances. This review examines the available evidence for and against the view that environmental PCBs represent a significant potential carcinogen to humans. This evidence is interpreted on the basis of mechanistic analysis of the biological processes involved in chemical carcinogenesis. This analysis suggests that much of the evidence for potential carcinogenicity of PCBs in experimental systems leads to a substantial overestimate of the real risks to humans exposed to environmental levels of PCBs.


Mutagenic Effect Chemical Carcinogenesis Genotoxic Carcinogen Polluted Aquatic Environment Genotoxic Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Jensen S (1966) New Scientist. 32:612Google Scholar
  2. 2.
    Risebrough RW, Rieche P, Herman SG, Peakall DB, Kirven MN (1968) Nature. London 220:1098CrossRefGoogle Scholar
  3. 3.
    Price HA, Welch RL (1972) Environ. Health Perspect. 1:73Google Scholar
  4. 4.
    Wasserman M, Wasserman D, Cucos S, Miller HJ (1979) Ann. N.Y. Acad. Sci. 320:69Google Scholar
  5. 5.
    Brinkman UATh, de Kok A (1980) In: Kimbrough RD (ed) Halogenated Biphenyls, Ter-phenyls, Naphthalenes, Dibenzodioxins and Related Products. Elsevier/North Holland, Amsterdam, p 1Google Scholar
  6. 6.
    Atlas E, Giam CS (1981) Science. 211:163CrossRefGoogle Scholar
  7. 7.
    Safe S (1984) CRC Crit. Rev. Toxicol. 13:319CrossRefGoogle Scholar
  8. 8.
    Tiernan JO, Taylor ML, Garrett JH, Van Ness GF, Solch JG, Wagel DJ, Ferguson GL, Schecter A (1985) Environ. Health Perspect. 59:143Google Scholar
  9. 9.
    Kikuchi M, Masuda Y (1976) In: Higuchi K (ed) PCB Poisoning and Pollution. Academic Press, New York, p 69Google Scholar
  10. 10.
    Masuda Y, Yoshimura H (1984) Am. J. Indust. Med. 5:31Google Scholar
  11. 11.
    Kikuchi M (1984) Am. J. Indust. Med. 5:19Google Scholar
  12. 12.
    Urabe H, Asahi M (1985) Environ. Health Perspect. 59:11CrossRefGoogle Scholar
  13. 13.
    Hsu S-T, Ma C-I, Hsu SK-H, Wu S-S, Hsu NH-M, Yeh C-C (1984) Am. J. Indust. Med. 5:71Google Scholar
  14. 14.
    Chen P, Wong C-K, Rappe C, Nygren M (1985) Environ. Health Perspect. 60:59CrossRefGoogle Scholar
  15. 15.
    Allen JR, Norback DH (1977) In: Hiatt HH, Watson JD, Winsten JA (eds) Origins of Human Cancer. Vol. 4. Cold Spring Harbor, New York, p 173Google Scholar
  16. 16.
    Kimbrough R, Buckley J, Fishbein L, Flamm G, Kasza L, Marcus W, Shibko S, Teske R (1978) Environ. Health Perspect. 24:173CrossRefGoogle Scholar
  17. 17.
    DiCarlo FJ, Seifter J, DeCarlo VJ (1978) Environ. Health Perspect. 23:351CrossRefGoogle Scholar
  18. 18.
    Kee N (1983) Nature. London 303:653Google Scholar
  19. 19.
    Kimbrough RD (1985) Environ. Health Perspect. 59:99CrossRefGoogle Scholar
  20. 20.
    Griem H, Wolff T (1984) ACS Monogr. 182:525Google Scholar
  21. 21.
    Somers E (1979) Can. J. Publ. Health 70:388Google Scholar
  22. 22.
    Cordle F (1984) Regul. Pharmacol. Toxicol. 4:236Google Scholar
  23. 23.
    Ito N, Nagasaki H, Arai M, Makiura S, Sugihara S, Hirao K (1973) J. Natl. Cancer Instit. 51:1637Google Scholar
  24. 24.
    Nishizumi M (1976) Cancer Lett. 2:11CrossRefGoogle Scholar
  25. 25.
    Kimura NT, Kanematsu T, Baba T (1976) Z. Krebsforsch. 87:257CrossRefGoogle Scholar
  26. 26.
    Kimbrough RD, Linder RE (1974) J. Natl. Cancer Instit. 53:547Google Scholar
  27. 27.
    Kimbrough RD, Squire RA, Linder RE, Strandberg JD, Montali RJ, Burse VW (1975) J. Natl. Cancer Instit. 55:1453Google Scholar
  28. 28.
    National Cancer Institute, Bethesda, MD (1977) CAS No. 27323–18–8 National Technical Information Service, Springfield Virginia, USA PB–279, 624/IGA, NCI–CG–TR–38 DHEW/Pubs/NIH–78–838Google Scholar
  29. 29.
    Tatematsu M, Nakanishi K, Murasaki G, Miyata Y, Hirose M, Ito N (1979) J. Natl. Cancer Instit. 63:1411Google Scholar
  30. 30.
    Ito N, Tatematsu M, Nakanishi K, Hasegawa R, Takano T, Imaida K (1980) Gann. 71:580Google Scholar
  31. 31.
    Preston BD, Van Miller JP, Moore RW, Allen JR (1981) J. Natl. Cancer Instit. 66:509Google Scholar
  32. 32.
    Becker F (1982) Cancer: A Comprehensive Treatise. 2nd Edit. Vol. 1, Plenum Co., New YorkGoogle Scholar
  33. 33.
    Ames BN, McCann J, Yamasaki E (1975) Mutat. Res. 31:347Google Scholar
  34. 34.
    de Serres FJ, Ashby J (1981) Evaluation of Short-term Tests for Carcinogens: Report of the International Collaborative Program. Elsevier/North HollandGoogle Scholar
  35. 35.
    Farber E, Cameron RG (1980) Adv. Cancer Res. 31:125CrossRefGoogle Scholar
  36. 36.
    Farber E (1984) Cancer Res. 44:4217Google Scholar
  37. 37.
    Pitot HC, Sirica AE (1980) Biochem. Biophys. Acta. 605:149Google Scholar
  38. 38.
    Boutwell RK (1974) CRC Crit Rev. Toxicol. 2:419CrossRefGoogle Scholar
  39. 39.
    Slaga TJ, Fischer SM, Nelson K, Gleason GA (1980) Proc. Natl. Acad. Sci. USA 77:659Google Scholar
  40. 40.
    Hicks RM, Chowaniec J (1978) Int. Rev. Exp. Pathol. 18:199Google Scholar
  41. 41.
    Witschi HR, Morse CC (1983) J. Natl. Cancer Instit. 71:859Google Scholar
  42. 42.
    Yokoro K, Nakano M, Ito A, Nagao K, Kodama Y, Hamada K (1977) J. Natl. Cancer Instit. 58:1777Google Scholar
  43. 43.
    Longnecker DS, Crawford BG (1975) J. Natl. Cancer Instit. 35:2249Google Scholar
  44. 44.
    Schulte-Hermann R (1985) Arch. Toxicol. 57:147CrossRefGoogle Scholar
  45. 45.
    Solt DB, Farber E (1976) Nature, London 263:701CrossRefGoogle Scholar
  46. 46.
    Tsuda H, Lee G, Farber E (1980) Cancer Res. 40:1157Google Scholar
  47. 47.
    Farber E (1984) Cancer Res. 44:5463Google Scholar
  48. 48.
    Moore MA, Hacker H-J, Bannasch P (1983) Carcinogenesis. 4:595CrossRefGoogle Scholar
  49. 49.
    Enomoto K, Farber E (1982) Cancer Res. 42:2330Google Scholar
  50. 50.
    Solt DB, Cayama E, Tsuda H, Enomoto K, Lee G, Farber E (1983) Cancer Res. 43:188Google Scholar
  51. 51.
    Miller EC (1978) Cancer Res. 38:1479Google Scholar
  52. 52.
    Rajalakshmi S, Rao P, Sarma DSR (1982) In: Becker F (ed) Cancer: A Comprehensive Treatise. Vol. 1. 2nd Edit. Plenum Co., New York, p 335Google Scholar
  53. 53.
    Tatematsu M, Nagamine Y, Farber E (1983) Cancer Res. 43:5049Google Scholar
  54. 54.
    Cayama E, Tsuda H, Sarma DSR, Farber E (1978) Nature, London 275:60CrossRefGoogle Scholar
  55. 55.
    Columbano A, Rajalakshmi S, Sarma DSR (1981) Cancer Res. 41:2079Google Scholar
  56. 56.
    Ying TS, Sarma DSR, Farber E (1981) Cancer Res. 41:2096Google Scholar
  57. 57.
    Hayes MA, Roberts E, Farber E (1985) Cancer Res. 45:3726Google Scholar
  58. 58.
    Neal GE, Butler WH (1978) Br. J. Cancer 37:55CrossRefGoogle Scholar
  59. 59.
    Tatematsu M, Hasegawa R, Imaida K, Tsuda H, Ito N (1983) Carcinogenesis. 4:381CrossRefGoogle Scholar
  60. 60.
    Peraino C, Fry RJM, Staffeldt E (1971) Cancer Res. 31:1506Google Scholar
  61. 61.
    Hennings H, Shores R, Wenk ML, Spangler EF, Tarone R, Yuspa SH (1983) Nature, London 304:67CrossRefGoogle Scholar
  62. 62.
    Pitot HC, Goldsworthy T, Moran S, Sirica AE, Weeks J (1982) In: Hecker E (ed) Carcinogenesis: A Comprehensive Survey, Vol. 7. Raven Press, New York, p 85Google Scholar
  63. 63.
    Ghoshal AK, Ahluwahlia M, Farber E (1983) Am. J. Pathol. 113:309Google Scholar
  64. 64.
    Pound AW, McGuire LJ (1978) Br. J. Cancer 37:595CrossRefGoogle Scholar
  65. 65.
    Roomi MW, Ho RK, Sarma DSR, Farber E (1985) Cancer Res. 45:564Google Scholar
  66. 66.
    Ogawa K, Medline A, Farber E (1979) Lab Investig. 41:22Google Scholar
  67. 67.
    Rotstein JR, Farber E (1986) Cancer Res.Google Scholar
  68. 68.
    Hayes MA, Roberts E, Dugan FP Cancer Res. Submitted for publicationGoogle Scholar
  69. 69.
    Mori H, Furuya H, Williams GM (1983) J. Natl. Cancer Instit. 71:849Google Scholar
  70. 70.
    Hayes MA, Lee G, Tatematsu M, Farber E (1987) Int. J. Cancer. In PressGoogle Scholar
  71. 71.
    Ward JM (1983) J. Natl. Cancer Instit. 71:815Google Scholar
  72. 72.
    Ho RK, Mishkin S, Farber E (1982) Proc. Amer. Assoc. Cancer Res. 23:52Google Scholar
  73. 73.
    Oesterle D, Deml E (1984) Carcinogenesis 5:351CrossRefGoogle Scholar
  74. 74.
    Hayes MA, Safe SH, Armstrong D, Cameron RG (1985) J. Natl. Cancer Instit. 74:1037Google Scholar
  75. 75.
    Berry DL, Slaga TJ, DiGiovanni J, Juchau MR (1979) Ann. N.Y. Acad. Sci. 320:405Google Scholar
  76. 76.
    Morales NM, Matthews HB (1979) Chem. Biol. Interact. 27:99CrossRefGoogle Scholar
  77. 77.
    Hargraves WA, Allen JR (1979) Res. Commun. Chem. Pathol. Pharmacol. 25:543Google Scholar
  78. 78.
    Preston BD, Miller JA, Miller EC (1983) J. Biol. Chem. 258:8304Google Scholar
  79. 79.
    Wong A, Basrur PK, Safe SH (1979) Res. Commun. Chem. Pathol. Pharmacol. 24:543Google Scholar
  80. 80.
    Stadnicki S, Lin FSD, Allen JR (1979) Res. Commun. Chem. Pathol. Pharmacol. 24:313Google Scholar
  81. 81.
    Hsia MT, Lin FS, Allen JR (1978) Res. Commun. Chem. Pathol. Pharmacol. 21:485Google Scholar
  82. 82.
    Schoeny R (1982) Mutat. Res. 10:45Google Scholar
  83. 83.
    Kimbrough RD, Linder RE, Gaines TB (1972) Arch. Environ. Health. 25:354Google Scholar
  84. 84.
    Ito N, Nagasaki H, Makiura S, Arai M (1974) Gann. 65:545Google Scholar
  85. 85.
    Nagasaki H, Tornii S, Mega T, Marugami M, Ito N (1972) Gann. 68:805Google Scholar
  86. 86.
    Kimura NT, Baba T (1973) Gann. 64:105Google Scholar
  87. 87.
    Schaeffer E, Greim H, Goessner W (1984) Toxicol. Appl. Pharmacol. 75:278CrossRefGoogle Scholar
  88. 88.
    Norback DH, Weltman RH (1985) Environ. Health Perspect. 60:97CrossRefGoogle Scholar
  89. 89.
    Morgan RW, Ward JM, Hartman PE (1981) Cancer Res. 41:5052Google Scholar
  90. 90.
    Ward JM (1985) Environ. Health Perspect. 60:89CrossRefGoogle Scholar
  91. 91.
    Schulte-Hermann R, Timmerman-Troisiener I, Schuppler J (1983) Cancer Res. 43:839Google Scholar
  92. 92.
    Alvares AP, Kappas A (1977) Clin. Pharmacol. Therap. 22:809Google Scholar
  93. 93.
    Hollstein M, McCann J, Angelosanto FA, Nichols WW (1979) Mutat. Res. 65:133Google Scholar
  94. 94.
    Deml E, Oesterle D, Wiebel FJ (1983) Cancer Lett. 19:301CrossRefGoogle Scholar
  95. 95.
    Anderson LM, Van Havere K, Budinger JM (1983) J. Natl. Cancer Instit. 71:157Google Scholar
  96. 96.
    Shelton DW, Hendricks JD, Bailey GS (1984) Toxicol. Lett. 22:27CrossRefGoogle Scholar
  97. 97.
    Nishizumi M (1980) Gann. 71:910Google Scholar
  98. 98.
    Makiura S, Aoe H, Sugihara S, Hirao K, Arai M, Ito N (1974) J. Natl. Cancer Instit. 53:1253Google Scholar
  99. 99.
    Hendricks JD, Putnam TP, Bills DD, Sinhuber RO (1977) J. Natl. Cancer Instit. 59:1545Google Scholar
  100. 100.
    Shelton DW, Hendricks JD, Coulombe RA, Bailey GS (1984) J. Toxicol. Environ. Health 13:649CrossRefGoogle Scholar
  101. 101.
    Bigger CAH, Tomaszewski JE, Dipple A, Lake RS (1980) Science. 209:503CrossRefGoogle Scholar
  102. 102.
    Hongslo J, Haug LT, Wirth PJ, Moller M, Dybing E, Thorgiersson SS (1983) Mutat. Res. 107:239CrossRefGoogle Scholar
  103. 103.
    Kohli KK, Mukhtar H, Bend JR, Albro PW, McKinney JD (1979) Biochem. Pharmacol. 28:1444CrossRefGoogle Scholar
  104. 104.
    Sharma RN, Cameron RG, Farber E, Griffen MJ, Joly JG, Murray RK (1979) Biochem. J. 183:317Google Scholar
  105. 105.
    Ahotupa M (1981) Biochem. Pharmacol. 30:1866CrossRefGoogle Scholar
  106. 106.
    Parkinson A, Safe SH, Robertson LW, Thomas PE, Ryan DE, Reik LM, Levin W (1983) J. Biol. Chem. 58:5967Google Scholar
  107. 107.
    Hayes MA, Roberts E, Roomi MW, Safe SH, Farber E, Cameron RG (1984) Toxicol. Appl. Pharmacol. 76:118CrossRefGoogle Scholar
  108. 108.
    Hayes MA, Roberts E, Safe SH, Farber E, Cameron RG (1986) J. Natl. Cancer Instit. 16:683Google Scholar
  109. 109.
    Mitchell JR, Hughes H, Lauterburg BH, Smith CV (1982) Drug Metab. Rev. 13:539CrossRefGoogle Scholar
  110. 110.
    Farber JL, Gerson RJ (1984) Pharmacol. Rev. 36:715Google Scholar
  111. 111.
    Pereira MA, Herren SL, Britt AL, Khoury MM (1982) Cancer Lett. 15:185CrossRefGoogle Scholar
  112. 112.
    Pitot HC, Goldsworthy T, Moran S, Sirica AE, Weeks J (1982) Carcinogenesis. 7:85Google Scholar
  113. 113.
    Sleight S (1985) Environ. Health Perspect 60:35CrossRefGoogle Scholar
  114. 114.
    Hirose M, Shirai T, Tsuda H, Fukushima S, Ogiso T, Ito N (1981) Carcinogenesis. 2:1299CrossRefGoogle Scholar
  115. 115.
    Collins WT, Capen CC, Kasza L, Carter C, Dailey RE (1977) Amer. J. Pathol. 89:119Google Scholar
  116. 116.
    Collins WT, Capen CC (1980) Virchows Arch. B. Cell Path. 33:213CrossRefGoogle Scholar
  117. 117.
    Diwan BA, Palmer AE, Ohshima M, Rice JM (1985) J. Natl. Cancer Instit. 75:1099Google Scholar
  118. 118.
    Hiasa Y, Kitahori Y, Oshima M, Fujita T, Yuasa T, Konishi N, Miyashiro A (1982) Carcinogenesis 3:1187CrossRefGoogle Scholar
  119. 119.
    Alvares AP, Kappas A (1977) J. Biol. Chem. 252:6373Google Scholar
  120. 120.
    Alvares AP, Kappas A (1975) FEBS Lett. 50:172CrossRefGoogle Scholar
  121. 121.
    Wong TK, Everson RB, Hsu ST (1985) Lancet 1:721CrossRefGoogle Scholar
  122. 122.
    Ueng T-H, Alvares AP (1985) Toxicology 35:83CrossRefGoogle Scholar
  123. 123.
    Lake BG, Collins MA, Harris RA, Gangoli SD (1979) Xenobiotica. 9:723CrossRefGoogle Scholar
  124. 124.
    Allen JR (1975) Fed. Proc. 34:1675Google Scholar
  125. 125.
    McConnell EE, Hass JR, Altman N, Moore JAA (1979) Lab. Anim. Sci. 29:666Google Scholar
  126. 126.
    Schulte-Hermann R (1974) CRC Crit. Rev. Toxicol. 3:97CrossRefGoogle Scholar
  127. 127.
    Schulte-Hermann R, Parzefall W (1981) Cancer Res. 41:4140Google Scholar
  128. 128.
    Ito N, Tsuda H, Hasegawa R, Imaida K (1983) Environ. Health Perspect. 50:131CrossRefGoogle Scholar
  129. 129.
    Reddy JK, Lalwai ND (1983) CRC Crit. Rev. Toxicol. 12:11CrossRefGoogle Scholar
  130. 130.
    Lans M, de Gerlache J, Taper HS, Preat V, Roberfroid M (1983) Carcinogenesis 4:141CrossRefGoogle Scholar
  131. 131.
    Columbano A, Ledda G, Rao PM, Rajalakshmi S, Sarma DSR (1984) Amer. J. Pathol. 116:441Google Scholar
  132. 132.
    Williams GM (1981) Food Cosmet. Toxicol. 19:577CrossRefGoogle Scholar
  133. 133.
    McLean AEM, Marshall A (1971) Br. J. Exp. Pathol. 52:322Google Scholar
  134. 134.
    Flaks A, Flaks B (1982) Carcinogenesis 3:381CrossRefGoogle Scholar
  135. 135.
    Hayes MA (1983) Proc. Amer. Assoc. Cancer Res. 24:338Google Scholar
  136. 136.
    Hayes MA, Cameron RG, Roberts E, Safe S, Farber E (1984) Proc. Amer. Assoc. Cancer Res. 25:505Google Scholar
  137. 137.
    Thorgiersson SS, Erickson LC, Smith CL, Glowinski IB (1983) Environ. Health Perspect. 49:141CrossRefGoogle Scholar
  138. 138.
    Haseman JK (1983) Fund. Appl. Toxicol. 3:1CrossRefGoogle Scholar
  139. 139.
    Roe FJC (1983) Nature. 303:657CrossRefGoogle Scholar
  140. 140.
    Clemmeson J, Fuglsang-Fredriksen V, Plum CM (1974) Lancet 1:705CrossRefGoogle Scholar
  141. 141.
    Clemmeson J, Hjalgrim-Jensen S (1978) Ecotoxicol. Environ. Safety. 1:457CrossRefGoogle Scholar
  142. 142.
    Tschirley FH (1986) Scientific American 254:29CrossRefGoogle Scholar
  143. 143.
    Roberts DW (1982) J. Amer. Med. Assoc. 247:2142CrossRefGoogle Scholar
  144. 144.
    Wolff MS, Anderson HA, Selikoff IT (1982) J. Amer. Med. Assoc. 247:2112CrossRefGoogle Scholar
  145. 145.
    Moseley CL, Geraci CL, Burg J (1982) Amer. J. Ind. Hygiene 43:170CrossRefGoogle Scholar
  146. 146.
    Mes J, Davies DJ, Turton D (1982) Bull. Environ. Contam. Toxicol. 28:97CrossRefGoogle Scholar
  147. 147.
    Unger M, Olsen J, Clausen J (1982) Environ. Res. 29:371CrossRefGoogle Scholar
  148. 148.
    Brown DP, Jones M (1981) Arch. Environ. Health 36:120Google Scholar
  149. 149.
    Cammarano G, Crosignani P, Berrino F, Berra G (1984) Scand. J. Work. Environ. Health 10:259CrossRefGoogle Scholar
  150. 150.
    Couch JA, Harshbarger JC (1985) Environ. Carcinogenesis Res. 3:63CrossRefGoogle Scholar
  151. 151.
    Mix MC (1985) Mar. Environ. Res. (In press)Google Scholar
  152. 152.
    Malins DC, McCain BB, Brown DW, Chan S, Meyers MS, Landahl JT, Prohaska PG, Friedman AJ, Rhodes DG (1984) Environ. Sci. Technol. 18:705CrossRefGoogle Scholar
  153. 153.
    Maxim LD, Harrington L (1984) Regul. Toxicol. Pharmacol. 4:192CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of PathologyUniversity of GuelphGuelphCanada

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