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Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences.
Groups of hairless mice were treated with 4 skin applications of 470 nmol 3-methylcholanthrene (MCA) in benzene and 4 of 20 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) in various sequences, twice a week, together and separately. Three days after the last application, cell kinetic investigations...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1982
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011048/ https://www.ncbi.nlm.nih.gov/pubmed/7093124 |
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author | Iversen, O. H. Iversen, U. M. |
author_facet | Iversen, O. H. Iversen, U. M. |
author_sort | Iversen, O. H. |
collection | PubMed |
description | Groups of hairless mice were treated with 4 skin applications of 470 nmol 3-methylcholanthrene (MCA) in benzene and 4 of 20 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) in various sequences, twice a week, together and separately. Three days after the last application, cell kinetic investigations were made comprising the counting of basal and suprabasal cells, the assessment of hyperplasia, the mitotic rate by the stathmokinetic method, the labelling index and the specific activity of DNA after injection of a dose of [3H]dT, and the determination of percentage of cells in each cell-cycle phase by flow cytometry. These studies showed that various treatment schedules with 4 applications stimulated proliferation and caused epidermal hyperplasia, but there was no significant difference between the groups in degree of growth stimulation. There was a significantly higher tumour production by all the combinations than by MCA alone. It was of no significant importance for the tumour production whether the 4 applications of MCA came before or after the 4 of TPA. Alternating treatment (MCA-TPA, etc.) seemed to give a higher tumour risk than the other treatment sequences. The consequences of these results for the two-stage theory of carcinogenesis (stating that initiation must come first) are discussed, and it is concluded that (at least under the experimental conditions used here) initiation does not need to come first for a good tumour yield. |
format | Text |
id | pubmed-2011048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1982 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-20110482009-09-10 Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. Iversen, O. H. Iversen, U. M. Br J Cancer Research Article Groups of hairless mice were treated with 4 skin applications of 470 nmol 3-methylcholanthrene (MCA) in benzene and 4 of 20 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) in various sequences, twice a week, together and separately. Three days after the last application, cell kinetic investigations were made comprising the counting of basal and suprabasal cells, the assessment of hyperplasia, the mitotic rate by the stathmokinetic method, the labelling index and the specific activity of DNA after injection of a dose of [3H]dT, and the determination of percentage of cells in each cell-cycle phase by flow cytometry. These studies showed that various treatment schedules with 4 applications stimulated proliferation and caused epidermal hyperplasia, but there was no significant difference between the groups in degree of growth stimulation. There was a significantly higher tumour production by all the combinations than by MCA alone. It was of no significant importance for the tumour production whether the 4 applications of MCA came before or after the 4 of TPA. Alternating treatment (MCA-TPA, etc.) seemed to give a higher tumour risk than the other treatment sequences. The consequences of these results for the two-stage theory of carcinogenesis (stating that initiation must come first) are discussed, and it is concluded that (at least under the experimental conditions used here) initiation does not need to come first for a good tumour yield. Nature Publishing Group 1982-06 /pmc/articles/PMC2011048/ /pubmed/7093124 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Iversen, O. H. Iversen, U. M. Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title | Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title_full | Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title_fullStr | Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title_full_unstemmed | Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title_short | Must initiators come first? Tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and TPA in various sequences. |
title_sort | must initiators come first? tumorigenic and carcinogenic effects on skin of 3-methylcholanthrene and tpa in various sequences. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2011048/ https://www.ncbi.nlm.nih.gov/pubmed/7093124 |
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