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Article: The effect of N-methyl-N'-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cells

TitleThe effect of N-methyl-N'-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cells
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date1997
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 1997, v. 26 n. 5, p. 1296-1302 How to Cite?
AbstractNormal dog gallbladder epithelial cells in long-term culture were used as a model to study the morphologic, genetic, and secretory processes associated with the progression to cancer formation. Dog gallbladder epithelial cells cultured on collagen-coated plates grew into polarized monolayers, could be passaged repeatedly, and showed the typical morphological profile of well-differentiated columnar epithelial cells. After cells were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 10-5 mol/L for 48 hours, the treated cells grew on plastic and could be cloned. Flow cytometry revealed emergence of an aneuploid cell subpopulation. In organotypic culture, treated cells showed a pseudostratified appearance, with cellular and nuclear pleomorphism. Large and hyperchromatic nuclei were present as well as increased mitotic rate. The proteins of MNNG-treated dog gallbladder epithelial cells showed increased phosphorylation of tyrosine residues. Treated cells showed a decrease in mucin secretion in response to prostaglandin E2, manifesting an altered pattern of mucin secretion. Transforming growth factor-beta failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibition in normal cells. Together, the data reflected changes representing preliminary steps on the pathway to develop cancer cells. Our results indicate that carcinogenic chemicals can cause measurable chromosomal and cellular modifications to normal biliary epithelial cells in vitro. This model may be useful in understanding the sequential steps in carcinogenesis and affords an opportunity to study chromosomal damage, cytokinetics, changes in molecular genetic markers, and expression, as well as cell biological function during cellular transformation.
Persistent Identifierhttp://hdl.handle.net/10722/92489
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMalik, Ren_HK
dc.contributor.authorLee, SKen_HK
dc.contributor.authorSavard, CEen_HK
dc.contributor.authorOda, Den_HK
dc.contributor.authorWong, WSen_HK
dc.contributor.authorChan, BYen_HK
dc.contributor.authorLee, SPen_HK
dc.date.accessioned2010-09-17T10:47:49Z-
dc.date.available2010-09-17T10:47:49Z-
dc.date.issued1997en_HK
dc.identifier.citationHepatology, 1997, v. 26 n. 5, p. 1296-1302en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/92489-
dc.description.abstractNormal dog gallbladder epithelial cells in long-term culture were used as a model to study the morphologic, genetic, and secretory processes associated with the progression to cancer formation. Dog gallbladder epithelial cells cultured on collagen-coated plates grew into polarized monolayers, could be passaged repeatedly, and showed the typical morphological profile of well-differentiated columnar epithelial cells. After cells were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 10-5 mol/L for 48 hours, the treated cells grew on plastic and could be cloned. Flow cytometry revealed emergence of an aneuploid cell subpopulation. In organotypic culture, treated cells showed a pseudostratified appearance, with cellular and nuclear pleomorphism. Large and hyperchromatic nuclei were present as well as increased mitotic rate. The proteins of MNNG-treated dog gallbladder epithelial cells showed increased phosphorylation of tyrosine residues. Treated cells showed a decrease in mucin secretion in response to prostaglandin E2, manifesting an altered pattern of mucin secretion. Transforming growth factor-beta failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibition in normal cells. Together, the data reflected changes representing preliminary steps on the pathway to develop cancer cells. Our results indicate that carcinogenic chemicals can cause measurable chromosomal and cellular modifications to normal biliary epithelial cells in vitro. This model may be useful in understanding the sequential steps in carcinogenesis and affords an opportunity to study chromosomal damage, cytokinetics, changes in molecular genetic markers, and expression, as well as cell biological function during cellular transformation.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.titleThe effect of N-methyl-N'-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SP: sumlee@hku.hken_HK
dc.identifier.authorityLee, SP=rp01351en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid9362375-
dc.identifier.scopuseid_2-s2.0-0030684070en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030684070&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume26en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1296en_HK
dc.identifier.epage1302en_HK
dc.identifier.isiWOS:A1997YE98900031-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMalik, R=7201876476en_HK
dc.identifier.scopusauthoridLee, SK=7601392865en_HK
dc.identifier.scopusauthoridSavard, CE=6701738621en_HK
dc.identifier.scopusauthoridOda, D=7006186359en_HK
dc.identifier.scopusauthoridWong, WS=7403972145en_HK
dc.identifier.scopusauthoridChan, BY=36765900600en_HK
dc.identifier.scopusauthoridLee, SP=7601417497en_HK

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