The changes of epidermal lipid and calcium in the lesion of skin tumor and non-tumor of hairless mice induced by vinyl carbamate epoxide and TPA

Sung Ku Ahn, Hana Bak, Seung Hyun Chun, Soo Young Jeon, Eung Ho Choi, Sang Joo Lee, Seung Hun Lee

Research output: Contribution to journalArticle

Abstract

Background: Chemically induced epidermal carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. Ethyl carbamate (EC) has been identified at low microgram quantities in various fermented beverages, distilled products and tobacco smoke. It has been known as a initiator of tumor. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide (VCO). VC and VCO proved to be much more carcinogenic than EC. Object: This study is attemped to investigate the skin tumor and non-skin tumor in hairless mice induced by application of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the skin initiated with VCO and its relationship with calcium gradient and epidermal lipid. Methods: In this experiment, the tumor induction was performed by painting the mouse skin once a week for five weeks with VCO solution, and then 12-0-tetradecanoyl-phobol-13-acetate (TPA) was treated in the same manner twice a week for 40 weeks. We biopsied the skin at 5, 10, 25, 30, 35 and 40 weeks and stained the specimens with hematoxylin-eosin, Ru04 postfixation and ion capture cytochemistry for calcium staining. Results: The results are summerized as follows 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were more prominent in skin tumors than non-skin tumors. Papillomas were developed at 8 weeks after application of VCO-TPA but not TPA alone. The occurrence of keratoacanthoma and squamous cell carcinoma was 33 and 39 weeks, respectively. 2. Calcium gradient was distorted in the only TPA treatment group but normal in the control group. Calcium deposition was increased through all layers of epidermis and the calcium gradient was disappeared in the epidermis of tumors in the VCO-TPA treatment group. These findings were similar to papilloma, keratoacanthoma and squamous cell carcinoma. 3. Fragmented, incomplete lipid bilayer formation, dilated intercellular spaces and multiple lacunar domains were prominent in the VCO-TPA and TPA treatment groups but not in the control group. The VCO-TPA treatment group has shown more epidermal lipid damage than that of the only TPA treatment group. 4. Diploid DNA histogram patterns were observed in all the control and TPA treatment groups. But aneuploidy was observed in 1 of 3 keratoacanthomas and 3 of 3 squamous cell carcinomas. Conclusion: From the above results, it is concluded that various skin tumors, such as papilloma, keratoacanthoma and squamous cell carcinoma or non-skin tumor were produced by VCO. Skin tumors showed various, distinctive light microscopic or electron microscopic changes compared to the non-skin tumor. It is thought that intercellular lipid change and calcium gradient disappearance in the epidermis have an important role in the carcinogenesis.

Original languageEnglish
Pages (from-to)1304-1312
Number of pages9
JournalKorean Journal of Dermatology
Volume42
Issue number10
Publication statusPublished - 2004 Oct 1

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Hairless Mouse
Acetates
Calcium
Lipids
Skin
Keratoacanthoma
Neoplasms
Epidermis
Squamous Cell Carcinoma
Urethane
Papilloma
Carcinogens
Carcinogenesis
vinyl carbamate epoxide
phorbol
Therapeutics
Cell Proliferation
Histocytochemistry
Control Groups
Paintings

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

Ahn, Sung Ku ; Bak, Hana ; Chun, Seung Hyun ; Jeon, Soo Young ; Choi, Eung Ho ; Lee, Sang Joo ; Lee, Seung Hun. / The changes of epidermal lipid and calcium in the lesion of skin tumor and non-tumor of hairless mice induced by vinyl carbamate epoxide and TPA. In: Korean Journal of Dermatology. 2004 ; Vol. 42, No. 10. pp. 1304-1312.
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abstract = "Background: Chemically induced epidermal carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. Ethyl carbamate (EC) has been identified at low microgram quantities in various fermented beverages, distilled products and tobacco smoke. It has been known as a initiator of tumor. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide (VCO). VC and VCO proved to be much more carcinogenic than EC. Object: This study is attemped to investigate the skin tumor and non-skin tumor in hairless mice induced by application of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the skin initiated with VCO and its relationship with calcium gradient and epidermal lipid. Methods: In this experiment, the tumor induction was performed by painting the mouse skin once a week for five weeks with VCO solution, and then 12-0-tetradecanoyl-phobol-13-acetate (TPA) was treated in the same manner twice a week for 40 weeks. We biopsied the skin at 5, 10, 25, 30, 35 and 40 weeks and stained the specimens with hematoxylin-eosin, Ru04 postfixation and ion capture cytochemistry for calcium staining. Results: The results are summerized as follows 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were more prominent in skin tumors than non-skin tumors. Papillomas were developed at 8 weeks after application of VCO-TPA but not TPA alone. The occurrence of keratoacanthoma and squamous cell carcinoma was 33 and 39 weeks, respectively. 2. Calcium gradient was distorted in the only TPA treatment group but normal in the control group. Calcium deposition was increased through all layers of epidermis and the calcium gradient was disappeared in the epidermis of tumors in the VCO-TPA treatment group. These findings were similar to papilloma, keratoacanthoma and squamous cell carcinoma. 3. Fragmented, incomplete lipid bilayer formation, dilated intercellular spaces and multiple lacunar domains were prominent in the VCO-TPA and TPA treatment groups but not in the control group. The VCO-TPA treatment group has shown more epidermal lipid damage than that of the only TPA treatment group. 4. Diploid DNA histogram patterns were observed in all the control and TPA treatment groups. But aneuploidy was observed in 1 of 3 keratoacanthomas and 3 of 3 squamous cell carcinomas. Conclusion: From the above results, it is concluded that various skin tumors, such as papilloma, keratoacanthoma and squamous cell carcinoma or non-skin tumor were produced by VCO. Skin tumors showed various, distinctive light microscopic or electron microscopic changes compared to the non-skin tumor. It is thought that intercellular lipid change and calcium gradient disappearance in the epidermis have an important role in the carcinogenesis.",
author = "Ahn, {Sung Ku} and Hana Bak and Chun, {Seung Hyun} and Jeon, {Soo Young} and Choi, {Eung Ho} and Lee, {Sang Joo} and Lee, {Seung Hun}",
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The changes of epidermal lipid and calcium in the lesion of skin tumor and non-tumor of hairless mice induced by vinyl carbamate epoxide and TPA. / Ahn, Sung Ku; Bak, Hana; Chun, Seung Hyun; Jeon, Soo Young; Choi, Eung Ho; Lee, Sang Joo; Lee, Seung Hun.

In: Korean Journal of Dermatology, Vol. 42, No. 10, 01.10.2004, p. 1304-1312.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The changes of epidermal lipid and calcium in the lesion of skin tumor and non-tumor of hairless mice induced by vinyl carbamate epoxide and TPA

AU - Ahn, Sung Ku

AU - Bak, Hana

AU - Chun, Seung Hyun

AU - Jeon, Soo Young

AU - Choi, Eung Ho

AU - Lee, Sang Joo

AU - Lee, Seung Hun

PY - 2004/10/1

Y1 - 2004/10/1

N2 - Background: Chemically induced epidermal carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. Ethyl carbamate (EC) has been identified at low microgram quantities in various fermented beverages, distilled products and tobacco smoke. It has been known as a initiator of tumor. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide (VCO). VC and VCO proved to be much more carcinogenic than EC. Object: This study is attemped to investigate the skin tumor and non-skin tumor in hairless mice induced by application of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the skin initiated with VCO and its relationship with calcium gradient and epidermal lipid. Methods: In this experiment, the tumor induction was performed by painting the mouse skin once a week for five weeks with VCO solution, and then 12-0-tetradecanoyl-phobol-13-acetate (TPA) was treated in the same manner twice a week for 40 weeks. We biopsied the skin at 5, 10, 25, 30, 35 and 40 weeks and stained the specimens with hematoxylin-eosin, Ru04 postfixation and ion capture cytochemistry for calcium staining. Results: The results are summerized as follows 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were more prominent in skin tumors than non-skin tumors. Papillomas were developed at 8 weeks after application of VCO-TPA but not TPA alone. The occurrence of keratoacanthoma and squamous cell carcinoma was 33 and 39 weeks, respectively. 2. Calcium gradient was distorted in the only TPA treatment group but normal in the control group. Calcium deposition was increased through all layers of epidermis and the calcium gradient was disappeared in the epidermis of tumors in the VCO-TPA treatment group. These findings were similar to papilloma, keratoacanthoma and squamous cell carcinoma. 3. Fragmented, incomplete lipid bilayer formation, dilated intercellular spaces and multiple lacunar domains were prominent in the VCO-TPA and TPA treatment groups but not in the control group. The VCO-TPA treatment group has shown more epidermal lipid damage than that of the only TPA treatment group. 4. Diploid DNA histogram patterns were observed in all the control and TPA treatment groups. But aneuploidy was observed in 1 of 3 keratoacanthomas and 3 of 3 squamous cell carcinomas. Conclusion: From the above results, it is concluded that various skin tumors, such as papilloma, keratoacanthoma and squamous cell carcinoma or non-skin tumor were produced by VCO. Skin tumors showed various, distinctive light microscopic or electron microscopic changes compared to the non-skin tumor. It is thought that intercellular lipid change and calcium gradient disappearance in the epidermis have an important role in the carcinogenesis.

AB - Background: Chemically induced epidermal carcinogenesis is usually divided into two stages, the initiation and promotion. The initiation involves conversion of some epidermal cells into latent neoplastic cells and the promotion is proliferation of the transformed cells. Ethyl carbamate (EC) has been identified at low microgram quantities in various fermented beverages, distilled products and tobacco smoke. It has been known as a initiator of tumor. Oxidation of the ethyl group of EC is followed by dehydration to yield the carcinogen vinyl carbamate (VC). This is further oxidized to vinyl carbamate epoxide (VCO). VC and VCO proved to be much more carcinogenic than EC. Object: This study is attemped to investigate the skin tumor and non-skin tumor in hairless mice induced by application of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the skin initiated with VCO and its relationship with calcium gradient and epidermal lipid. Methods: In this experiment, the tumor induction was performed by painting the mouse skin once a week for five weeks with VCO solution, and then 12-0-tetradecanoyl-phobol-13-acetate (TPA) was treated in the same manner twice a week for 40 weeks. We biopsied the skin at 5, 10, 25, 30, 35 and 40 weeks and stained the specimens with hematoxylin-eosin, Ru04 postfixation and ion capture cytochemistry for calcium staining. Results: The results are summerized as follows 1. Cellular proliferation, hyperkeratosis and dysplasia of the epidermis were more prominent in skin tumors than non-skin tumors. Papillomas were developed at 8 weeks after application of VCO-TPA but not TPA alone. The occurrence of keratoacanthoma and squamous cell carcinoma was 33 and 39 weeks, respectively. 2. Calcium gradient was distorted in the only TPA treatment group but normal in the control group. Calcium deposition was increased through all layers of epidermis and the calcium gradient was disappeared in the epidermis of tumors in the VCO-TPA treatment group. These findings were similar to papilloma, keratoacanthoma and squamous cell carcinoma. 3. Fragmented, incomplete lipid bilayer formation, dilated intercellular spaces and multiple lacunar domains were prominent in the VCO-TPA and TPA treatment groups but not in the control group. The VCO-TPA treatment group has shown more epidermal lipid damage than that of the only TPA treatment group. 4. Diploid DNA histogram patterns were observed in all the control and TPA treatment groups. But aneuploidy was observed in 1 of 3 keratoacanthomas and 3 of 3 squamous cell carcinomas. Conclusion: From the above results, it is concluded that various skin tumors, such as papilloma, keratoacanthoma and squamous cell carcinoma or non-skin tumor were produced by VCO. Skin tumors showed various, distinctive light microscopic or electron microscopic changes compared to the non-skin tumor. It is thought that intercellular lipid change and calcium gradient disappearance in the epidermis have an important role in the carcinogenesis.

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