Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung

Liang You, Dian Wang, Anthony J. Galati, Jeffrey A. Ross, Marc J. Mass, Garret B. Nelson, Katrina H. Wilson, Shantu Amin, Jason C. Stoner, Stephen Nesnow, Gary D. Stoner

Research output: Contribution to journalArticle

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Abstract

This study was undertaken to evaluate the carcinogenic potenlial of 5-methylchrysene (5-MeC) in strain A/J mouse lung and to correlate the 5-MeC-DNA adduct profile in lung tissue with the mutation spectrum in the K-ras gene of lung tumors. Strain A/J mice received a single i.p. injection of 5-MeC at doses of 10, 50, 100 and 200 mg/kg and after 24, 48 and 72 h their lungs were collected for DNA adduct analysis. Eight months later, lungs from the remaining mice were harvested and the lung tumors counted and collected for subsequent mutational analysis of the K-ras gene. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. Six 5-MeC-DNA adducts were observed; one adduct comigrated with the standard N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I [1R,2S,3S-trihydroxy-4R-(N2-deoxyguanosyl-3'-phosphate)-1,2,3,4-tetrahydro-5-methyl-chrysene], derived from the bay-region diol-epoxide of 5-MeC. DNAs isolated from 5-MeC-induced lung tumors were evaluated for activating mutations in the K-ras gene by polymerase chain reaction-single strand conformation polymorphism and direct DNA sequencing analysis. Mutations were detected in 44 of 49 (90%) 5-MeC-induced tumors and the mutations were GGT→TGT (50%), GGT→GTT (23%) and GGT→CGT (27%) in codon 12 of the gene. These results suggest that the N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I may be one of the promutagenic adducts of 5-MeC in strain A/J mouse lung. Oxford University Press.

Original languageEnglish (US)
Pages (from-to)2613-2618
Number of pages6
JournalCarcinogenesis
Volume15
Issue number11
DOIs
StatePublished - Nov 1 1994

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DNA Adducts
Lung
Mutation
Neoplasms
ras Genes
Epoxy Compounds
Deoxyguanosine
5-methylchrysene
DNA Sequence Analysis
Codon
Carcinogens
Phosphates
Polymerase Chain Reaction
Injections

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

You, L., Wang, D., Galati, A. J., Ross, J. A., Mass, M. J., Nelson, G. B., ... Stoner, G. D. (1994). Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung. Carcinogenesis, 15(11), 2613-2618. https://doi.org/10.1093/carcin/15.11.2613
You, Liang ; Wang, Dian ; Galati, Anthony J. ; Ross, Jeffrey A. ; Mass, Marc J. ; Nelson, Garret B. ; Wilson, Katrina H. ; Amin, Shantu ; Stoner, Jason C. ; Nesnow, Stephen ; Stoner, Gary D. / Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung. In: Carcinogenesis. 1994 ; Vol. 15, No. 11. pp. 2613-2618.
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title = "Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung",
abstract = "This study was undertaken to evaluate the carcinogenic potenlial of 5-methylchrysene (5-MeC) in strain A/J mouse lung and to correlate the 5-MeC-DNA adduct profile in lung tissue with the mutation spectrum in the K-ras gene of lung tumors. Strain A/J mice received a single i.p. injection of 5-MeC at doses of 10, 50, 100 and 200 mg/kg and after 24, 48 and 72 h their lungs were collected for DNA adduct analysis. Eight months later, lungs from the remaining mice were harvested and the lung tumors counted and collected for subsequent mutational analysis of the K-ras gene. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. Six 5-MeC-DNA adducts were observed; one adduct comigrated with the standard N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I [1R,2S,3S-trihydroxy-4R-(N2-deoxyguanosyl-3'-phosphate)-1,2,3,4-tetrahydro-5-methyl-chrysene], derived from the bay-region diol-epoxide of 5-MeC. DNAs isolated from 5-MeC-induced lung tumors were evaluated for activating mutations in the K-ras gene by polymerase chain reaction-single strand conformation polymorphism and direct DNA sequencing analysis. Mutations were detected in 44 of 49 (90{\%}) 5-MeC-induced tumors and the mutations were GGT→TGT (50{\%}), GGT→GTT (23{\%}) and GGT→CGT (27{\%}) in codon 12 of the gene. These results suggest that the N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I may be one of the promutagenic adducts of 5-MeC in strain A/J mouse lung. Oxford University Press.",
author = "Liang You and Dian Wang and Galati, {Anthony J.} and Ross, {Jeffrey A.} and Mass, {Marc J.} and Nelson, {Garret B.} and Wilson, {Katrina H.} and Shantu Amin and Stoner, {Jason C.} and Stephen Nesnow and Stoner, {Gary D.}",
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You, L, Wang, D, Galati, AJ, Ross, JA, Mass, MJ, Nelson, GB, Wilson, KH, Amin, S, Stoner, JC, Nesnow, S & Stoner, GD 1994, 'Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung', Carcinogenesis, vol. 15, no. 11, pp. 2613-2618. https://doi.org/10.1093/carcin/15.11.2613

Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung. / You, Liang; Wang, Dian; Galati, Anthony J.; Ross, Jeffrey A.; Mass, Marc J.; Nelson, Garret B.; Wilson, Katrina H.; Amin, Shantu; Stoner, Jason C.; Nesnow, Stephen; Stoner, Gary D.

In: Carcinogenesis, Vol. 15, No. 11, 01.11.1994, p. 2613-2618.

Research output: Contribution to journalArticle

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T1 - Tumor multiplicity, DNA adducts and K-ras mutation pattern of 5-methylchrysene in strain A/J mouse lung

AU - You, Liang

AU - Wang, Dian

AU - Galati, Anthony J.

AU - Ross, Jeffrey A.

AU - Mass, Marc J.

AU - Nelson, Garret B.

AU - Wilson, Katrina H.

AU - Amin, Shantu

AU - Stoner, Jason C.

AU - Nesnow, Stephen

AU - Stoner, Gary D.

PY - 1994/11/1

Y1 - 1994/11/1

N2 - This study was undertaken to evaluate the carcinogenic potenlial of 5-methylchrysene (5-MeC) in strain A/J mouse lung and to correlate the 5-MeC-DNA adduct profile in lung tissue with the mutation spectrum in the K-ras gene of lung tumors. Strain A/J mice received a single i.p. injection of 5-MeC at doses of 10, 50, 100 and 200 mg/kg and after 24, 48 and 72 h their lungs were collected for DNA adduct analysis. Eight months later, lungs from the remaining mice were harvested and the lung tumors counted and collected for subsequent mutational analysis of the K-ras gene. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. Six 5-MeC-DNA adducts were observed; one adduct comigrated with the standard N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I [1R,2S,3S-trihydroxy-4R-(N2-deoxyguanosyl-3'-phosphate)-1,2,3,4-tetrahydro-5-methyl-chrysene], derived from the bay-region diol-epoxide of 5-MeC. DNAs isolated from 5-MeC-induced lung tumors were evaluated for activating mutations in the K-ras gene by polymerase chain reaction-single strand conformation polymorphism and direct DNA sequencing analysis. Mutations were detected in 44 of 49 (90%) 5-MeC-induced tumors and the mutations were GGT→TGT (50%), GGT→GTT (23%) and GGT→CGT (27%) in codon 12 of the gene. These results suggest that the N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I may be one of the promutagenic adducts of 5-MeC in strain A/J mouse lung. Oxford University Press.

AB - This study was undertaken to evaluate the carcinogenic potenlial of 5-methylchrysene (5-MeC) in strain A/J mouse lung and to correlate the 5-MeC-DNA adduct profile in lung tissue with the mutation spectrum in the K-ras gene of lung tumors. Strain A/J mice received a single i.p. injection of 5-MeC at doses of 10, 50, 100 and 200 mg/kg and after 24, 48 and 72 h their lungs were collected for DNA adduct analysis. Eight months later, lungs from the remaining mice were harvested and the lung tumors counted and collected for subsequent mutational analysis of the K-ras gene. 5-MeC was found to be a potent lung carcinogen in strain A/J mice, inducing more than 100 tumors/mouse at a concentration of 200 mg/kg. Six 5-MeC-DNA adducts were observed; one adduct comigrated with the standard N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I [1R,2S,3S-trihydroxy-4R-(N2-deoxyguanosyl-3'-phosphate)-1,2,3,4-tetrahydro-5-methyl-chrysene], derived from the bay-region diol-epoxide of 5-MeC. DNAs isolated from 5-MeC-induced lung tumors were evaluated for activating mutations in the K-ras gene by polymerase chain reaction-single strand conformation polymorphism and direct DNA sequencing analysis. Mutations were detected in 44 of 49 (90%) 5-MeC-induced tumors and the mutations were GGT→TGT (50%), GGT→GTT (23%) and GGT→CGT (27%) in codon 12 of the gene. These results suggest that the N2-deoxyguanosine adduct of 5-MeC-diol-epoxide I may be one of the promutagenic adducts of 5-MeC in strain A/J mouse lung. Oxford University Press.

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