|
Sign In to gain access to subscriptions and/or personal tools.
|
Demonstration of a Temporal Relationship Between Ethyl Acrylate-Induced Forestomach Cell Proliferation and Carcinogenicity
Burhan I. Ghanayem
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Idalia M. Sanchez
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
H.B. Matthews
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Michael R. Elwell
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Ethyl acrylate (EA) is a known forestomach carcinogen in both rats and mice. Recent work in this laboratory indicated that carcinogenic doses of EA administered by gavage for 13 wk resulted in a sustained increase in forestomach epithelial hyperplasia as long as exposure to EA continued. However, hyperplasia regressed and no forestomach neoplasms were seen after a 19-mo recovery period. Current studies were designed to further investigate the time required for sustained hyperplasia to lead to neoplasia as well as the organ specificity of EA-induced cell proliferation/hyperplasia vs carcinogenicity. EA was administered at 200 mg/ kg (po) to male Fischer-344 rats, 5 days/wk. Squamous cell proliferation/hyperplasia was observed in the forestomach of all rats that received EA for 6 or 12 mo. Treatment of rats with EA for 12 mo followed by 2 mo of recovery resulted in the development of forestomach papillomas in 2 of 5 treated rats. Furthermore, animals treated for 12 mo and allowed 9 mo of recovery exhibited an increase in forestomach squamous cell carcinomas and papillomas at a combined incidence of 4 in 13. In contrast, animals treated with EA for 6 mo and allowed 2 or 15 mo of recovery exhibited a time-dependent regression of cell proliferation and did not develop forestomach neoplasms. No significant elevation in liver cell proliferation or neoplasia was seen at any time in any of the rats included in the present study, further confirming the organ specificity in the relationship between EA-induced cell proliferation and carcinogenicity. In conclusion, EA resulted in increased cell proliferation in the target organ of carcinogenicity (forestomach) but not in nontarget organs such as the liver. This work indicates that cell proliferation, sustained for a sufficient period of time, results in the development of neoplasia despite cessation of chemical administration. Furthermore, a temporal relationship exists between EA-induced epithelial cell proliferation and forestomach carcinogenicity.
Key Words: Male Fischer-344 rats • sustainability • reversibility • carcinogenesis
- Ames BN and Gold LS (1991). Mitogenesis, mutagenesis, and animal cancer tests. In: Chemically Induced Cell Proliferation: Implications for Risk Assessment, BE Butterworth. TJ Slaga, W Farland, and M McClain (eds). Wiley-Liss. New York. pp. 1-20.
- Ames BN, Profet M., and Gold LS (1990). Nature's chemicals and synthetic chemicals. Proc. Natl. Acad. Sci. USA 87: 7782-7786.[Abstract/Free Full Text]
- Ashby J., Richardson CR, and Tinwell H. (1989). Inactivity of ethyl acrylate in the mouse bone marrow micronucleus assay. Mutagenesis 4: 283-285.[Abstract/Free Full Text]
- Chadwick RW, George SE, and Claxton LD (1992). Role of the gastrointestinal mucosa and microflora in the bioactivation of the dietary and environmental mutagens or carcinogens. Drug Metab. Rev. 24: 425-492.[Web of Science][Medline]
[Order article via Infotrieve]
- Cohen SM and Ellwein LB (1990). Cell proliferation and carcinogenesis. Science 249: 1007-1011.[Abstract/Free Full Text]
- Cohen MS and Ellwein LB (1991). Genetic errors, cell proliferation, and carcinogenesis. Cancer Res. 51: 6493-6505.[Free Full Text]
- Cohen SM, Ellwein LB, and Johansson SL (1987). Bladder tumor promotion. In: Nongenotoxic Mechanisms of Carcinogenesis, Banbury Report 25, BE Butterworth and TJ Slaga (eds). Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, pp. 25-29.
- DeBethizy JD, Udinskey JR, Scribner HE, and Frederick CB (1987). The disposition of acrylic acid and ethyl acrylate in male Sprague-Dawley rats. Fund. Appl. Toxicol. 8: 549-561.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Eldrige SR, Tilbury LF, Goldsworthy TL, and Butterworth BE (1991). Measurement of chemically-induced cell proliferation in rodent liver and kidney: A comparison of 5-bromo-2'-deoxyuridine and [H3]-thymidine administered by injection or osmotic pump. Carcinogenesis 11: 2245-2251.[CrossRef][Web of Science]
- Frederick CB, Hazelton GA, and Frantz JD (1990). The histopathological and biochemical response of the stomach of male F344/N rats following two weeks of oral dosing with ethyl acrylate. Toxicol. Pathol. 18: 247-256.[Web of Science][Medline]
[Order article via Infotrieve]
- Frederick CB, Potter DW, Chang-Mateu MI, and Anderson ME (1992). A physiologically based pharmacokinetics and pharmacodynamics model to describe the oral dosing of rats with ethyl acrylate and its implications for risk assessment. Toxicol. Appl. Pharmacol. 114: 246-260.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ghanayem BI, Burka LT, and Matthews HB (1987). Ethyl acrylate distribution, macromolecular binding, excretion, and metabolism in male Fisher 344 rats. Fund. Appl. Toxicol. 9: 389-397.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ghanayem BI, Maronpot RR, and Matthews HB (1986). Association of chemically induced cell proliferation and carcinogenesis. Cancer Lett. 32: 271-278.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ghanayem BI, Maronpot RR, and Matthews HB (1985). Ethyl acrylate induced gastric toxicity: II. Structure-toxicity relationships and mechanism. Toxicol. Appl. Pharmacol. 80: 336-344.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ghanayem BI, Maronpot RR and Matthews HB (1986). Ethyl acrylate induced gastric toxicity: III. Development and recovery of lesions. Toxicol. Appl. Pharmacol. 83: 576-583.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ghanayem BI, Matthews HB, and Maronpot RR (1991). Sustainability of forestomach hyperplasia in rats treated with ethyl acrylate for 13 weeks and regression after cessation of dosing. Toxicol. Pathol. 19: 273-279.[Web of Science][Medline]
[Order article via Infotrieve]
- Hirose M., Inoue T., Asamoto M., Tagawa Y., and Ito N. (1986). Comparison of the effects of 13 phenolic compounds in induction of proliferative lesions of the forestomach and increase in the labeling indices of the glandular stomach and urinary bladder epithelium of Syrian golden hamsters. Carcinogenesis 7: 1285-1289.[Abstract/Free Full Text]
- Hirose M., Yamaguchi S., Fukushima S., Hasegawa R., Takahashi S., and Ito N. (1989). Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine induced F344 rat forestomach and glandular stomach carcinogenesis. Cancer Res. 49: 5143-5147.[Abstract/Free Full Text]
- Iarc ( 1986). Some chemicals used in plastics and elastomers. IARC Monogr. Ecal. Carcinog. Risk Chem. Humans 39: 67-112.
- Ito N., Fukushima S., Hagiwara A., Shibata M., and Ogiso T. (1983). Carcinogenicity of butylated hydroxyanisole in Fischer 344 rats. J. Natl. Cancer Inst. 70: 343-352.[Web of Science][Medline]
[Order article via Infotrieve]
- Kagawa M., Fukushima S., de Camargo JL, Ogawa K., and Hirose M. (1988). Comparison of the reversibility of rat forestomach lesions induced by genotoxic and nongenotoxic carcinogens. Proc. Jpn. J. CancerAssoc. 47: 88-94.
- Kaufman WK, Rihija RJ, MacKenzie SA, and Kaufman DG (1987). Cell cycle-dependent initiation of hepatocarcinogenesis in rats by (±)-7r,8t-dihydroxy-9t, 1 0t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Cancer Res. 47: 3771-3775.[Abstract/Free Full Text]
- Loeb LA (1989). Endogenous carcinogenesis: Molecular oncology into the twentieth century-Presidential address. Cancer Res. 49: 5489-5496.[Free Full Text]
- Marsman DS, Cattley RC, Conway JG, and Popp JA (1988). Relationship of hepatic peroxisome proliferation and replicative DNA synthesis to the hepatocarcinogenicity of the peroxisome proliferators di(2-ethylhexyl)phthalate and [4-chloro-6- (2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643) in rats. Cancer Res. 48: 6739-6744.
- Monticello MT, Morgan KT, Everitt JI, and Popp JA (1989 ). Effects of formaldehyde gas on the respiratory tract of Rhesus monkeys: Pathology and cell proliferation. Am. J. Pathol. 134: 515-527.[Abstract]
- Moore MM, Antower A., Doerr CL, Brock KH, and Dearfield KL (1988). Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate and ethyl methacrylate in L5178Y mouse lymphoma cells. Environ. Mol. Mutagen 11: 49-63.[Web of Science][Medline]
[Order article via Infotrieve]
- National Toxicology Program ( 1986). Carcinogenesis Bioassay of Ethyl Acrylate. Technical Report Series No. 259, Publication (NIH) 82-2515, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
- Nera EA, Iverson F., Lok E., Armstrong CL, Karpinski K., and Clayson DB (1987). A carcinogenesis reversibility study of the effects of butylated hydroxyanisole on the forestomach and urinary bladder in male Fischer 344 rats. Toxicology 53: 251-268.[CrossRef]
- Popp JA and Marsman DS ( 1991). Chemically induced cell proliferation in liver carcinogenesis. In: Chemically Induced Cell Proliferation: Implications for Risk Assessment, BE Butterworth. TJ Slaga, W Farland, and M McClain (eds). Wiley-Liss, New York, pp. 389-395.
- Przybojewska B., Dziubaltowska E., and Kowalski Z. (1984). Genotoxic effects of ethyl acrylate and methyl acrylate in the mouse evaluated by the micronucleus test. Mutation Res. 135: 189-191.[CrossRef][Medline]
[Order article via Infotrieve]
- Short BG, Burnett VL, and Swenberg JA (1989). Elevated proliferation of proximal tubule cells and localization of accumulated
 .2u-globulin in F344 rats during chronic exposure to unleaded gasoline or 2,2,4-trimethylpentane. Toxicol. Appl. Pharmacol. 101: 414-431.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve] - Sugihara H., Hattori T., and Fukuda M. (1986). Immunohistochemical detection of bromodeoxyuridine in formalin-fixed tissues. Histochemistry 85: 193-195.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Swenberg AJ and Maronpot RR (1991). Chemically induced cell proliferation as a criterion in selecting doses for long term bioassays. In: Chemically Induced Cell Proliferation: Implications for Risk Assessment, BE Butterworth. TJ Slaga, W Farland. and M McClain (eds). Wiley-Liss, New York. pp. 245-251.
- Tatematsu M. Ogawa K. Mutai M. Aoki T. Hoshiya T. and Ito N. (1991). Rapid regression of squamous cell hyperplasia and slow regression of basal cell hyperplasia in the forestomach of F344 rats treated with N-methyl-N-nitro-N-nitrosoguanidine and or butylated hydroxyanisole. Cancer Res. 51: 318-323.[Abstract/Free Full Text]
- Tenant RW, Margolin BH Shelby MD Zeiger E., Haseman JK, Splading J., Caspary W., Resnick M., Stasiewwics S., Anderson B., and Minor R. (1987). Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science 236: 933-941.[Abstract/Free Full Text]
- US Department of Health and Human Services, National Institutes of Health(1985). Guide of the Care and Use of Laboratory Animals. NIH Publication No. 86-23, US Department of Health and Human Services, Washington, D.C.
- Waegemakers Thjm and Bensik MPM (1984). Nonmutagenicity of 27 aliphatic acrylate esters in Salmonella-microsome test. Mutation Res. 137: 95-102.[CrossRef][Medline]
[Order article via Infotrieve]
Toxicologic Pathology, Vol. 22, No. 5,
497-509 (1994)
DOI: 10.1177/019262339402200504
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
D. M. Proctor, N. M. Gatto, S. J. Hong, and K. P. Allamneni
Mode-of-Action Framework for Evaluating the Relevance of Rodent Forestomach Tumors in Cancer Risk Assessment
Toxicol. Sci.,
August 1, 2007;
98(2):
313 - 326.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Ghanayem
Inhibition of Urethane-Induced Carcinogenicity in Cyp2e1-/- in Comparison to Cyp2e1+/+ Mice
Toxicol. Sci.,
February 1, 2007;
95(2):
331 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. I. Ghanayem, A. Nyska, J. K. Haseman, and J. R. Bucher
Acrylonitrile Is a Multisite Carcinogen in Male and Female B6C3F1 Mice
Toxicol. Sci.,
July 1, 2002;
68(1):
59 - 68.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Winner, R. A. Prough, and M. D. Brennan
Human NAD(P)H:Quinone Oxidoreductase Induction in Human Hepatoma Cells after Exposure to Industrial Acrylates, Phenolics, and Metals
Drug Metab. Dispos.,
February 1, 1997;
25(2):
175 - 181.
[Abstract]
[Full Text]
|
|
|
|
|
