Reference SummaryHong HH, Toxicol Pathol 2007;35(1):81-5
Title |
K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse. |
Authors |
Hong HH; Houle CD; Ton TV; Sills RC |
Journal |
Toxicol Pathol |
Volume |
35 |
Issue |
1 |
Year |
2007 |
Pages |
81-5 |
Abstract |
Ethylene oxide is a multisite carcinogen in rodents and classified as a human carcinogen by the National Toxicology Program. In 2-year mouse studies, ethylene oxide (EO) induced lung, Harderian gland (HG), and uterine neoplasms. We evaluated representative EO-induced and equivalent spontaneous neoplasms for K-ras mutations in codons 12, 13, and 61. K-ras mutations were identified in 100% (23/23) of the EO-induced lung neoplasms and 25% (27/108) of the spontaneous lung neoplasms. Codon 12 G to T transversions were common in EO-induced lung neoplasms (21/23) but infrequent in spontaneous lung neoplasms (1/108). K-ras mutations were found in 86% (18/21) of the EO-induced HG neoplasms and 7% (2/27) of the spontaneous HG neoplasms. Codon 13 G to C and codon 12 G to T transversions were predominant in the EO-induced HG neoplasms but absent in spontaneous HG neoplasms (0/27). K-ras mutations occurred in 83% (5/6) of the EO-induced uterine carcinomas and all were codon 13 C to T transitions. These data show a strong predilection for development of K-ras mutations in EO-induced lung, Harderian gland, and uterine neoplasms. This suggests that EO specifically targets the K-ras gene in multiple tissue types and that this event is a critical component of EO-induced tumorigenesis. |
Links |
J:129340 – MGI References 17325976 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| (C57BL/6 x C3H)F1 | Eye - Eyelid cystadenocarcinoma |
|
Eye - Harderian gland |
0 - 2.17 |
|
| (C57BL/6 x C3H)F1 | Eye - Harderian gland cystadenocarcinoma | Eye - Harderian gland |
0 |
||
| (C57BL/6 x C3H)F1 | Eye - Harderian gland cystadenocarcinoma |
|
Eye - Harderian gland |
0 - 2.38 |
|
| (C57BL/6 x C3H)F1 | Eye - Harderian gland cystadenoma | Eye - Harderian gland |
2.17 - 2.33 |
||
| (C57BL/6 x C3H)F1 | Eye - Harderian gland cystadenoma |
|
Eye - Harderian gland |
13.04 - 20.45 |
|
| (C57BL/6 x C3H)F1 | Eye - Harderian gland neoplasm |
|
Eye - Harderian gland |
observed |
|
| (C57BL/6 x C3H)F1 | Eye - Harderian gland neoplasm | Eye - Harderian gland |
observed |
||
| (C57BL/6 x C3H)F1 | Lung adenoma | Lung |
4.08 - 10 |
||
| (C57BL/6 x C3H)F1 | Lung adenoma |
|
Lung |
8.33 - 34.69 |
|
| (C57BL/6 x C3H)F1 | Lung carcinoma | Lung |
0 - 12 |
||
| (C57BL/6 x C3H)F1 | Lung carcinoma |
|
Lung |
2.08 - 32 |
|
| (C57BL/6 x C3H)F1 | Lung neoplasm |
|
Lung |
observed |
|
| (C57BL/6 x C3H)F1 | Lung neoplasm | Lung |
observed |
||
| (C57BL/6 x C3H)F1 | Uterus carcinoma | Uterus |
0 |
||
| (C57BL/6 x C3H)F1 | Uterus carcinoma |
|
Uterus |
observed - 10.20 |