Abstract
Acrylamide is a monomer of polyacrylamide, used in biochemistry, in paper manufacture, in water treatment, and as a soil stabilizer. The monomer can cause several toxic effects and has the potential for human exposure either through the environment or from occupational exposure. Recently, additional concern for the potential toxicity of acrylamide in humans has arisen with the finding of acrylamide formation in some processed foods. It has been established that following chronic exposure, rats exhibited an increase in the incidence of adrenal pheochromocytomas, testicular mesotheliomas, thyroid adenomas and mammary neoplasms in F344 rats. This has raised increased concerns regarding the carcinogenic risk to humans from acrylamide exposure. Studies examining the DNA reactivity of acrylamide have been performed and have had differing results. The tissue and organ pattern of neoplastic development seen in the rat following acrylamide exposure is not consistent with that seen with other strictly DNA reactive carcinogens. Based on the pattern of neoplastic development, it appears that acrylamide is targeting endocrine sensitive tissues. In the current monograph, studies on the effect of acrylamide on DNA reactivity and on altered cell growth in the target tissues in the rat are reported. DNA synthesis was examined in F344 rats treated with acrylamide (0, 2, or 15 mg/kg/day) for 7, 14, or 28 days. Acrylamide increased DNA synthesis in the target tissues (thyroid, testicular mesothelium, adrenal medulla) at all doses and time points examined. In contrast, in a non-target tissue (liver), no increase in DNA synthesis was seen. Examination of DNA damage using single cell gel electrophoresis (the Comet assay) showed an increase in DNA damage in the target tissues, but not in non-target tissue (liver). In addition, a cellular transformation model, (the Syrian Hamster Embryo (SHE) cell morphological transformation model), was used to examine potential mechanisms for the observed carcinogenicity of acrylamide. SHE cell studies showed that glutathione (GSH) modulation by acrylamide was important in the cell transformation process. Treatment with a sulfhydryl donor compound (NAC) reduced acrylamide transformation while depletion of GSH (BSO) resulted in an enhancement of transformation. In summary, acrylamide caused both an increase in DNA synthesis and DNA damage in mammalian tissues and cells suggesting that DNA reactivity and cell proliferation, in concert, may contribute to the observed acrylamide-induced carcinogenicity in the rat and has implication on the possible risk for human neoplasm development.
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References
Ames, B. N., and Gold, L. S., 1990, Chemical carcinogenesis: Too many rodent carcinogens, Proc. Natl. Acad. Sci. USA 87:7772–7776.
Agrawal, A.K., Seth, P. K., Squibb, R.E., Tilson, H. A., Uphouse, L. L., and Bondy, S. C., 1981, Neurotransmitter receptors in brain regions of acrylamide-treated rats. I: Effects of a single exposure to acrylamide, Pharmacol. Biochem. Behav. 14:527–531.
Banerjee, S., and Segal, A., 1986, In vitro transformation of C3H/10T1/2 and NIH/3T3 cells by acrylonitrile and acrylamide, Cancer Lett. 32:293–304.
Barfknecht, T., Mecca, D., and Naismith, B., 1988, The genotoxic activity of acrylamide, Environ. Mol. Mutagen. 11(Suppl. 11):9.
Barrett, J. C., Hesterberg, T. W., and Thomassen, D. G., 1984, Use of cell transformation systems for carcinogenicity testing and mechanistic studies of carcinogenesis, Pharmacol. Rev. 36:53s–7
Butterworth, B. E., and Goldsworthy, T. L., 1991. The role of cell proliferation in multi-stage carcinogenesis, Proc. Soc. Exp. Biol. Med. 198:683–687.
Cohen, S. M., and Ellwein, L. B., 1990, Cell proliferation in carcinogenesis, Science 249:1007–1011.
Cohen, S. M., and Ellwein, L. B., 1991, Genetic errors, cell proliferation, and carcinogenesis, Cancer Res. 51:6393–6505.
Dearfield, K., Douglas, G., Ehling, U., Moore, M., Sega, G., and Brusick, D., 1995, Acrylamide: a review of its genotoxicity and an assessment of heritable genetic risk, Mutation Res. 330:71–99.
Dumont, J. E., Lamy, F., Roger, P., and Maenhaut, C., 1992, Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors, Physiol. Rev. 72:667–697.
Eldridge, S. R., Tilbury, L. F., Goldsworthy, T. L., and Butterworth, B. E., 1990, Measurement of chemically induced cell proliferation in rodent liver and kidney: a comparison of 5-bromo-2’-deoxyuridine and [3H]-thymidine administered by injection or osmotic pump, Carcinogenesis 11:2245–2251.
Friedman, M. A., Dulak, L., and Stedham, M., 1995, A lifetime oncogenicity study in rats with acrylamide, Fundam. Appl. Toxicol. 27:95–105.
Gad, S., and Weil, C. S., 1986, Statistics and Experimental Design for Toxicologists, Telford Press: New Jersey.
Gibson, D. P., Aardema, M. J., Kerckaert, G. A., Carr, G. J. Brauniger, R. M. and LeBoeuf R. A., 1995, Detection of aneuploidy-inducing carcinogens in the Syrian hamster embryo (SHE) cell transformation assay, Mutat. Res. 343:7–24.
Isfort, R. J., Cody, D. B., Doersen, C. J., Kerckaert, G. A., and LeBoeuf, R. F., 1994, Alterations in cellular differentiation, mitogenesis, cytoskeleton and growth characteristics during Syrian hamster embryo cell multistep in vitro transformation, Int. J. Cancer 59:114–125.
Johnson, K. A., Gorzinski, S. J., Bodner, K. M., Campbell, R. A., Wolf, C. H., Friedman, M. A., and Mast, R. W., 1986, Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats, Toxicol. Appl. Pharmacol. 85:154–168.
Kerckaert, G. A., Isfort, R. J., Carr, G. J., Aardema, M. J., and LeBoeuf, R. A., 1996, A comprehensive protocol for conducting the Syrian hamster embryo cell transformation assay at pH 6.70, Mutat. Res. 356:65–84.
Klaunig, J. E., 1993, Selective induction of DNA synthesis in mouse preneoplastic and neoplastic hepatic lesions after exposure to phenobarbital, Environ. Health Perspect. 101 235–249.
Knaap, A., Kramers, P., Voogd, C., Bergkamp, W., Groot, M., Langerbroek, P., Mout, H., van der Stel, J., and Verharen, H., 1988, Mutagenic activity of acrylamide in eukaryotic systems but not in bacteria, Mutagenesis 3:263–268.
Lafferty, J. S., Kamendulis, L. M., Kaster, J, Jiang, J., and Klaunig, J. E., 2004, Subchronic acrylamide treatment induces a tissue-specific increase in DNA synthesis in the rat, Toxicol. Letts, in press.
Lapadula, D., Bowe, M., Carrington, C., Dulak, L., Friedman, M., and Abou-Donia, M., 1989, In Vitro binding of [14C] acrylamide to neurofilament and microtubule proteins of rats, Brain Res. 481:157–161.
Liaw, L., and Schwartz, S. M., 1993, Microtubule disruption stimulates DNA synthesis in bovine endothelial cells and potentiates cellular response to basic fibroblast growth factor, Am. J. Pathol. 143:937–948.
Moore, M., Amtower, A., Doerr, C., Brock, K., and Dearfield, K., 1987, Mutagenicity and clastogenicity of acrylamide in L5178Y mouse lymphoma cells, Environ. Mutagenesis 9:261–267.
National Institute for Occupational Safety and Health (NIOSH), 1976, Criteria for a recommended standard-Occupational exposure to acrylamide, Publication No. 77-112, DHHS (NIOSH): Washington, DC.
Park, J., Kamendulis, L. M., and Klaunig, J. E., 2002, Acrylamide-induced cellular transformation, Toxicol. Sci. 65:177–183.
Pienta, K. J., and Coffey, D. S., 1992, Nuclear-cytoskeletal interaction: evidence for physical connections between the nucleus and cell periphery and their alteration by transformation, J. Cell Biochem. 49:357–365.
Rojas, E., Lopez, M. C. and Valverde, M., 1999, Single cell gel electrophoresis assay: methodology and applications, J Chromatogr B Biomed Sci Appl, 722:225–54
Rosen J., and Hellenas K. E., 2002, Analysis of acrylamide in cooked foods by liquid chromatography tandem mass spectrometry, Analyst 127:880–882.
Schulte-Hermann, R., 1987, Tumor promotion in the liver, Arch Toxicol. 57:147–158.
Sega, G., Generoso, E., and Brimer, P., 1990, Acrylamide exposure induces a delayed unscheduled DNA synthesis in germ cells of male mice that is correlated with the temporal pattern of adduct formation in testis DNA, Environ. Mol. Mutagen. 16:137–142.
Shimoi, K., Okitsu, A., Green, M. H. L., Lowe, J. E., Ohta, T., Kaji, K., Terato, K., Ide, H., and Kinae, N., 2001, Oxidative DNA damage induced by high glucose and its suppression in human umbilical vein endothelial cells, Mutat. Res. 480:371–378.
Shiraishi, Y., 1978, Chromosome aberrations induced by monomeric actylamide in bone marrow and germ cells of mice, Mutat. Res. 57:313–324.
Srivastava, S. P., Sabri, M. I., Agrawal, A. K., and Seth, P. K., 1986, Effect of single and repeated doses of acrylamide and bis-acrylamide on glutathione-S-transferase and dopamine receptors in rat brain, Brain Res. 371:319–323.
Sumner, S. C. J., Fennell, T. R., Moore, T. A., Chanas, B, Gonzalez, F., and Ghanayem, B.I., 1999, Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice, Chem. Res. Toxicol. 12:1110–1116.
Tareke E., Rydberg P., Karlsson P., Eriksson S., and Tornqvist M., 2000, Acrylamide: a cooking carcinogen? Chem. Res. Toxicol. 13(6):517–22.
Tice, R.R. and Strauss, G. H., 1995, The single cell gel electrophoresis/comet assay: a potential tool for detecting radiation-induced DNA damage in humans, Stem Cells 13(Suppl 1):207–14.
Tsuda, H., Shimizu, C., Taketomi, M., Hasegawa, M., Hamada, A., Kawata, K., and Inui, N., 1993, Acrylamide; induction of DNA damage, chromosomal aberrations, and cell transformation without gene mutations, Mutagenesis 8:23–29.
Tsutsui, T., and Barrett, J. C., 1997, Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals, Environ. Health Perspect. 105(Suppl 3):619–624.
Tsutsui, T., Hayashi, N., Maizumi, H., Huff, J., and Barrett, J. C., 1997, Benzene-, catechol-, hydroquinone-, and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells, Mutat. Res. 373:113–123.
United States Environmental Protection Agency, 1994, Chemicals in the Environment: Acrylamide (CAS No. 79-06-01).
Weiss, G., 2002, Acrylamide in Food: Uncharted territory, Science 297:27.
World Health Organization, 1985, Acrylamide, Environmental Health Criteria 49.
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Klaunig, J.E., Kamendulis, L.M. (2005). Mechanisms of Acrylamide Induced Rodent Carcinogenesis. In: Friedman, M., Mottram, D. (eds) Chemistry and Safety of Acrylamide in Food. Advances in Experimental Medicine and Biology, vol 561. Springer, Boston, MA. https://doi.org/10.1007/0-387-24980-X_4
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DOI: https://doi.org/10.1007/0-387-24980-X_4
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