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Rodent studies have shown that patterns in chemical\u2010induced mutations in the hypoxanthine\u2010guanine phosphoribosyltransferase (<jats:italic>Hprt<\/jats:italic>) gene of T\u2010cells differ between lymphoid organs. The current work was performed to obtain knowledge of the relationships between maturation events during T\u2010cell development and changes in chemical\u2010induced mutant frequencies over time in differing immune compartments of a mouse model. A novel reverse transcriptase\u2010polymerase chain reaction based method was developed to determine the specific T\u2010cell receptor beta (<jats:italic>Tcrb<\/jats:italic>) gene mRNA expressed in mouse T\u2010cell isolates, enabling sequence analysis of the PCR product that then identifies the specific hypervariable CDR3 junctional region of the expressed <jats:italic>Tcrb<\/jats:italic> gene for individual isolates. Characterization of spontaneous <jats:italic>Hprt<\/jats:italic> mutant isolates from the thymus, spleen, and lymph nodes of control mice for their <jats:italic>Tcrb<\/jats:italic> gene expression found evidence of in vivo clonal amplifications of <jats:italic>Hprt<\/jats:italic> mutants and their trafficking between tissues in the same animal. Concurrent analyses of <jats:italic>Hprt<\/jats:italic> mutations and <jats:italic>Tcrb<\/jats:italic> gene rearrangements in different lymphoid tissues of control versus <jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea\u2010exposed mice permitted elucidation of the localization and timing of mutational events in T\u2010cells, establishing that mutagenesis occurs primarily in the pre\u2010rearrangement replicative period in pre\u2010thymic\/thymic populations. These findings demonstrate that chemical\u2010induced mutagenic burden is determined by the combination of mutagenesis and T\u2010cell clonal expansion, processes with roles in immune function and in the pathogenesis of autoimmune disease and cancer.<\/jats:p>","DOI":"10.1002\/em.22579","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T04:39:20Z","timestamp":1699936760000},"page":"432-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clonality, trafficking, and molecular alterations among <i>Hprt<\/i> mutant T lymphocytes isolated from control mice versus mice treated with <i>N<\/i><scp>\u2010ethyl\u2010<\/scp><i>N<\/i>\u2010nitrosourea"],"prefix":"10.1002","volume":"64","author":[{"given":"Stephen A.","family":"Judice","sequence":"first","affiliation":[{"name":"Genetic Toxicology Laboratory University of Vermont  Burlington Vermont USA"},{"name":"EnviroLogix  Portland Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary E.","family":"Sussman","sequence":"additional","affiliation":[{"name":"School of Public Health University at Albany \u2013 SUNY  Albany New York USA"},{"name":"New York State Department of Health Wadsworth Center  Albany New York USA"},{"name":"Cold Spring Harbor Laboratory Press  Cold Spring Harbor New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Experimental Pathology Laboratories  Sterling Virginia USA"},{"name":"The Burlington HC Research group, Inc.  Jericho Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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