The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase

Nitrosoureas form O6-alkylguanine-DNA adducts that are converted to G to A transitions, the mutation found in the activated ras oncogenes of nitrosourea-induced mouse lymphomas and rat mammary tumors. These adducts are removed by the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Transgeni...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1993-01, Vol.259 (5092), p.219-222
Main Authors: DUMENCO, L. L, ALLAY, E, NORTON, K, GERSON, S. L
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
DNA Repair - genetics
Gene Expression
Humans
Lymphoma, T-Cell - chemically induced
Lymphoma, T-Cell - prevention & control
Medical sciences
Methylnitrosourea
Methyltransferases - genetics
Methyltransferases - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
O-Methylguanine-DNA Methyltransferase
RNA, Messenger - analysis
Thymus Neoplasms - chemically induced
Thymus Neoplasms - prevention & control
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Nitrosoureas form O6-alkylguanine-DNA adducts that are converted to G to A transitions, the mutation found in the activated ras oncogenes of nitrosourea-induced mouse lymphomas and rat mammary tumors. These adducts are removed by the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Transgenic mice that express the human homolog of this protein in the thymus were found to be protected from developing thymic lymphomas after exposure to N-methyl-N-nitrosourea. Thus, transgenic expression of a single human DNA repair gene is sufficient to block chemical carcinogenesis. The transduction of DNA repair genes in vivo may unravel mechanisms of carcinogenesis and provide therapeutic protection from known carcinogens.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.8421782