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MUTATION ANALYSIS OF THE PROTO-ONCOGENES Ki-RAS AND C-MYC IN THE SOFT TISSUE TUMORS OF THE RATS THAT WERE FORMED BY 3-METHYLCHOLANTHRENE IN VIVO

Year 2008, Issue: 017, 11 - 18, 15.12.2008

Abstract

Polisiklik aromatik hidrokarbonlar en potent karsinojenler olarak bilinmektedir. 3-Metilkolantren PAH’ların

içinde yer alan karsinojenik bir ajandır. 3-Metilkolantren’in memeli sistemlerinde deneysel olarak toksik ve

karsinojenik etkileri gösterilmiştir. Bu bileşiklere çevrede zift, kurum, sıvı ve katı yakıtlar nedeniyle havada,

ekzos gazında, sigara dumanında, dumanlanmış yiyeceklerde sıklıkla rastlanmaktadır. Bu çalışmanın amacı 3-

Metilkolantren’ in 40 mg/kg’lık bir dozda kronik olarak ratlara verilmesiyle oluşan tümörlerde Ki-ras ekson 1, 2

ve C-myc ekson 2 genlerinde herhangi bir mutasyona neden olup olmadığını tespit etmektir. Ratlar son

enjeksiyondan 26 hafta sonra servikal dislokasyon ile öldürüldü ve oluşan yumuşak doku tümörleri çıkarıldı.

Dokular belirtilen genler için PCR tabanlı SSCP analiziyle incelendi. Sonuç olarak Ki-ras ekson 1, 2 ve C-myc

ekson 2 genlerinde hiçbir nokta mutasyonu görülmedi.

References

  • [1] Gressani, M.K., Rollins, L.A., Kabler, S.L., Cline, J.M., Miller, M.S., “ Induction of mutations in ki-ras and Ink4a in liver tumors of mice exposed in utero to 3-methylcholanthrene”, Carcinogenesis., 19: 1045- 1052 (1998).
  • [2] Gressani, M.K., Kabler S.L., O’sullivan M.G., Case, L.D., Malkinson, A.M., Miller, M.S., “Straindependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and postnatally exposed to butylated hydroxytoluene”, Carcinogenesis., 20: 2159-165 (1999).
  • [3] O'Donnell, E.P., Zerbe, L.K., Dwyer-Nield, L.D., Kisley, L.R., Malkinson, A.M., “Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis”,Cancer Lett 241:197-202, (2006).
  • [4] Riddick, D.S., “Transcriptional Supression of Cytochorome P4502C11 Gene Expression by 3-Methylcholanthrene”, Biochemical Pharmocology., 59:1417-1423 (2000).
  • [5] Ruddon R.W., “Cancer Biology”, Oxford University Press, New York, 42-44 (1995).
  • [6] Mcdonald, F., Ford, C.H.J., “Oncogenes and Tumor Supressor Genes”, Information Press. Oxford, 1-16 (1991).
  • [7] Cooper, G.M. “The Cell”, Asm Pres, Washington, 549-609 (2000).
  • [8] Algarra, I., Perez, M., Serreno, M.J., Garrido, F., Gafiro, J.J., “C-k-ras overexpression is characteristic for metastases derived from a methylcholantrene-ınduced fibrosarcoma”, Invasion and Metastasis., 18: 261-70 (1998).
  • [9] Watanabe, H., Shimokado, K., Asahara, T., Dohi, K., Niwa, O., “Analysis of the c-myc, k-ras and p53 genes in methylcholanthrene-induced mouse sarcomas”, Jpn.J. Cancer Res., 90: 40-47 (1999).
  • [10] Kabler, S.L., Wessner, L.L, MCentee, F., Agostino, R.B.D., Miller, M.S., “Ki-Ras mutations are an early event and correlate with tumor stage in transplacentally-ınduced murine lung tumors”, Carcinogenesis.,18: 1163-1168 (1997).
  • [11] Christoph, F., Schmidt, B., Schmitz-Drager, B.J., Schulz, W.A., “Over-expression and amplification of the c-myc gene in human urothelial carcinoma”, Int. J. Cancer (Pred. Oncol.)., 84: 169-173 (1999).
  • [12] Van Waardenburg, R.C.A.M., Meijer, C., Burger, H., Noter, K., De Vries, E.G.E., Mulder, N.H., De Jong, S., “Effects of an inducible anti-sense c-myc gne transfer in a drug-resistant human small-cell-lungcarcinoma cell line”, Int. J. Cancer., 73: 544-550 (1997).
  • [13] O'Leary, J.J., Landers, R.J., Crowley, M., Healy, I., Kealy, W.F., Hogan, J., Doyle, C.T., “Alterations in exon 1 of c-myc and expression of p62C-Myc in cervical squamous cell carcinoma”, J Clin Pathol., 50: 896-903 (1997).
  • [14] Ozdemir, O., Bulut, H., Korkmaz, M., Onarlioglu, B., Colak, A., “Increased cell proliferation and rmsp1 fragmentation in testicular tissue of rat induced by 5-aza-2'-deoxycytidine”. Exp And Toxic Pathol., 52:317-322 (2000).
  • [15] Hazardous Substance Fact Sheet. New Jersey Department of Health and Senior Services. August 1998.D.P.Ü. Fen Bilimleri Enstitüsü Mutation Analysis of the Proto-Oncogenes Ki-Ras and C-MYC in the Soft Tissue Tumors 17. Sayı Aralık 2008 of the Rats That Were Formed By 3-Methylcholanthrene in Vivo F.POLAT & N.TURAÇLAR & E.GÜL & Ö.ÖZDEMİR & G.BİNGÖL 17
  • [16] Maddox, C., Wang, B., Kirby, P.A., Wang, K., Ludewig, G., “Mutagenicity of 3-methylcholantherene,PCB3, and 4-OH-PCB3 in the lung of transgenic BigBlue® rats”, Environ Toxicol Pharmacol., 25: 260-266 (2008).
  • [17] Wesner, L. L., Fan, M., Scheffer, D. O., McEntee, F., Miller, M. S., “Mouse Lung Tumors Exhibit Specific Ki-ras Mutations Folloing Transplacental Exposure to 3-Methylcholanthrene”, Carcinogenesis.,7:1519-26 (1996).
  • [18] Niwa, O., Kamiya, K., Furihata, C., Nitta, Y., Wang, Z., Fan, Y. J., Ninomiya, Y., Kotomura, N.,Numoto, M., Kominami, R., “Association of Minisatellite Instability with c-myc Amplification and K-ras Mutation in Methylcholanthrene-Induced Mouse Sarcomas”, Cancer Res. 23: 5670-6 (1995).
  • [19] Niwa, O., Kominami, R., “Lack of allelic preference in amplification and loss of the c-myc oncogene in methylcholanthrene-induced mouse sarcomas”. Jpn J Cancer Res., 83:1192-7 (1992). [ 20] Niwa, O., Enoki, Y., Yokoro, K., “Overexpression and amplification of the c-myc gene in mouse tumors induced by chemicals and radiations”. Jpn J Cancer Res.80:212-8. (1989).
  • [21] Engström, W., Barrios, C., Willems, J.S., Möllermark, G., Kängström, L.E., Eliasson, I., Larsson, O., “Expression of the myc protooncogene in canine rhabdomyosarcoma”, Anticancer Res.,7:1109-10 (1987).
  • [22] Christie, N.T., Tummolo, D.M., Biggart, N.W., Murphy, E.C., “Chromosomal changes in cell lines from mouse tumors induced by nickel sulfide and methylcholanthrene”. Cell Biol Toxicol., 4: 427-45 (1988).
  • [23] Keshava, N., Keshava, C., Whong, W.Z., Hubbs, A.F., Nath, J., Ong, T., “Preneoplastic potential of morphologically distinct transformed foci induced by 3-methylcholanthrene”, Environ Mol Mutagen.,32:369-76(1998).

MUTATION ANALYSIS OF THE PROTO-ONCOGENES Ki-RAS AND C-MYC IN THE SOFT TISSUE TUMORS OF THE RATS THAT WERE FORMED BY 3-METHYLCHOLANTHRENE IN VIVO

Year 2008, Issue: 017, 11 - 18, 15.12.2008

Abstract

Polisiklik aromatik hidrokarbonlar en potent karsinojenler olarak bilinmektedir. 3-Metilkolantren PAH’ların

içinde yer alan karsinojenik bir ajandır. 3-Metilkolantren’in memeli sistemlerinde deneysel olarak toksik ve

karsinojenik etkileri gösterilmiştir. Bu bileşiklere çevrede zift, kurum, sıvı ve katı yakıtlar nedeniyle havada,

ekzos gazında, sigara dumanında, dumanlanmış yiyeceklerde sıklıkla rastlanmaktadır. Bu çalışmanın amacı 3-

Metilkolantren’ in 40 mg/kg’lık bir dozda kronik olarak ratlara verilmesiyle oluşan tümörlerde Ki-ras ekson 1, 2

ve C-myc ekson 2 genlerinde herhangi bir mutasyona neden olup olmadığını tespit etmektir. Ratlar son

enjeksiyondan 26 hafta sonra servikal dislokasyon ile öldürüldü ve oluşan yumuşak doku tümörleri çıkarıldı.

Dokular belirtilen genler için PCR tabanlı SSCP analiziyle incelendi. Sonuç olarak Ki-ras ekson 1, 2 ve C-myc

ekson 2 genlerinde hiçbir nokta mutasyonu görülmedi.

References

  • [1] Gressani, M.K., Rollins, L.A., Kabler, S.L., Cline, J.M., Miller, M.S., “ Induction of mutations in ki-ras and Ink4a in liver tumors of mice exposed in utero to 3-methylcholanthrene”, Carcinogenesis., 19: 1045- 1052 (1998).
  • [2] Gressani, M.K., Kabler S.L., O’sullivan M.G., Case, L.D., Malkinson, A.M., Miller, M.S., “Straindependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and postnatally exposed to butylated hydroxytoluene”, Carcinogenesis., 20: 2159-165 (1999).
  • [3] O'Donnell, E.P., Zerbe, L.K., Dwyer-Nield, L.D., Kisley, L.R., Malkinson, A.M., “Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis”,Cancer Lett 241:197-202, (2006).
  • [4] Riddick, D.S., “Transcriptional Supression of Cytochorome P4502C11 Gene Expression by 3-Methylcholanthrene”, Biochemical Pharmocology., 59:1417-1423 (2000).
  • [5] Ruddon R.W., “Cancer Biology”, Oxford University Press, New York, 42-44 (1995).
  • [6] Mcdonald, F., Ford, C.H.J., “Oncogenes and Tumor Supressor Genes”, Information Press. Oxford, 1-16 (1991).
  • [7] Cooper, G.M. “The Cell”, Asm Pres, Washington, 549-609 (2000).
  • [8] Algarra, I., Perez, M., Serreno, M.J., Garrido, F., Gafiro, J.J., “C-k-ras overexpression is characteristic for metastases derived from a methylcholantrene-ınduced fibrosarcoma”, Invasion and Metastasis., 18: 261-70 (1998).
  • [9] Watanabe, H., Shimokado, K., Asahara, T., Dohi, K., Niwa, O., “Analysis of the c-myc, k-ras and p53 genes in methylcholanthrene-induced mouse sarcomas”, Jpn.J. Cancer Res., 90: 40-47 (1999).
  • [10] Kabler, S.L., Wessner, L.L, MCentee, F., Agostino, R.B.D., Miller, M.S., “Ki-Ras mutations are an early event and correlate with tumor stage in transplacentally-ınduced murine lung tumors”, Carcinogenesis.,18: 1163-1168 (1997).
  • [11] Christoph, F., Schmidt, B., Schmitz-Drager, B.J., Schulz, W.A., “Over-expression and amplification of the c-myc gene in human urothelial carcinoma”, Int. J. Cancer (Pred. Oncol.)., 84: 169-173 (1999).
  • [12] Van Waardenburg, R.C.A.M., Meijer, C., Burger, H., Noter, K., De Vries, E.G.E., Mulder, N.H., De Jong, S., “Effects of an inducible anti-sense c-myc gne transfer in a drug-resistant human small-cell-lungcarcinoma cell line”, Int. J. Cancer., 73: 544-550 (1997).
  • [13] O'Leary, J.J., Landers, R.J., Crowley, M., Healy, I., Kealy, W.F., Hogan, J., Doyle, C.T., “Alterations in exon 1 of c-myc and expression of p62C-Myc in cervical squamous cell carcinoma”, J Clin Pathol., 50: 896-903 (1997).
  • [14] Ozdemir, O., Bulut, H., Korkmaz, M., Onarlioglu, B., Colak, A., “Increased cell proliferation and rmsp1 fragmentation in testicular tissue of rat induced by 5-aza-2'-deoxycytidine”. Exp And Toxic Pathol., 52:317-322 (2000).
  • [15] Hazardous Substance Fact Sheet. New Jersey Department of Health and Senior Services. August 1998.D.P.Ü. Fen Bilimleri Enstitüsü Mutation Analysis of the Proto-Oncogenes Ki-Ras and C-MYC in the Soft Tissue Tumors 17. Sayı Aralık 2008 of the Rats That Were Formed By 3-Methylcholanthrene in Vivo F.POLAT & N.TURAÇLAR & E.GÜL & Ö.ÖZDEMİR & G.BİNGÖL 17
  • [16] Maddox, C., Wang, B., Kirby, P.A., Wang, K., Ludewig, G., “Mutagenicity of 3-methylcholantherene,PCB3, and 4-OH-PCB3 in the lung of transgenic BigBlue® rats”, Environ Toxicol Pharmacol., 25: 260-266 (2008).
  • [17] Wesner, L. L., Fan, M., Scheffer, D. O., McEntee, F., Miller, M. S., “Mouse Lung Tumors Exhibit Specific Ki-ras Mutations Folloing Transplacental Exposure to 3-Methylcholanthrene”, Carcinogenesis.,7:1519-26 (1996).
  • [18] Niwa, O., Kamiya, K., Furihata, C., Nitta, Y., Wang, Z., Fan, Y. J., Ninomiya, Y., Kotomura, N.,Numoto, M., Kominami, R., “Association of Minisatellite Instability with c-myc Amplification and K-ras Mutation in Methylcholanthrene-Induced Mouse Sarcomas”, Cancer Res. 23: 5670-6 (1995).
  • [19] Niwa, O., Kominami, R., “Lack of allelic preference in amplification and loss of the c-myc oncogene in methylcholanthrene-induced mouse sarcomas”. Jpn J Cancer Res., 83:1192-7 (1992). [ 20] Niwa, O., Enoki, Y., Yokoro, K., “Overexpression and amplification of the c-myc gene in mouse tumors induced by chemicals and radiations”. Jpn J Cancer Res.80:212-8. (1989).
  • [21] Engström, W., Barrios, C., Willems, J.S., Möllermark, G., Kängström, L.E., Eliasson, I., Larsson, O., “Expression of the myc protooncogene in canine rhabdomyosarcoma”, Anticancer Res.,7:1109-10 (1987).
  • [22] Christie, N.T., Tummolo, D.M., Biggart, N.W., Murphy, E.C., “Chromosomal changes in cell lines from mouse tumors induced by nickel sulfide and methylcholanthrene”. Cell Biol Toxicol., 4: 427-45 (1988).
  • [23] Keshava, N., Keshava, C., Whong, W.Z., Hubbs, A.F., Nath, J., Ong, T., “Preneoplastic potential of morphologically distinct transformed foci induced by 3-methylcholanthrene”, Environ Mol Mutagen.,32:369-76(1998).
There are 22 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Articles
Authors

Fikriye Polat This is me

Nesrin Turaçlar This is me

Eylem Gül This is me

Öztürk Özdemir This is me

Günsel Bingöl This is me

Publication Date December 15, 2008
Published in Issue Year 2008 Issue: 017

Cite

APA Polat, F., Turaçlar, N., Gül, E., Özdemir, Ö., et al. (2008). MUTATION ANALYSIS OF THE PROTO-ONCOGENES Ki-RAS AND C-MYC IN THE SOFT TISSUE TUMORS OF THE RATS THAT WERE FORMED BY 3-METHYLCHOLANTHRENE IN VIVO. Journal of Science and Technology of Dumlupınar University(017), 11-18.

HAZİRAN 2020'den itibaren Journal of Scientific Reports-A adı altında ingilizce olarak yayın hayatına devam edecektir.