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Several single\u2010nucleotide polymorphisms (SNPs) have been described in the <jats:italic>ATM<\/jats:italic> gene; however, their association with cancer risk or radiosensitivity remains to be fully established. In this study, the functional consequences of specific <jats:italic>ATM<\/jats:italic> SNPs on in vitro radiosensitivity, as assessed by micronuclei (MN) formation, were measured in lymphoblastoid cell lines established from 10 breast cancer (BC) patients carrying different <jats:italic>ATM<\/jats:italic> missense SNPs, six A\u2010T patients, six A\u2010T heterozygotes (A\u2010T het), and six normal individuals. The BC, A\u2010T het, and A\u2010T cell line groups showed significantly higher mean levels of MN formation after exposure to ionizing radiation (IR) than did the group containing normal cell lines, with similar levels in the BC and A\u2010T het groups. Within the BC lines studied, the group composed of the six carrying the linked 2572T&gt;C (858F&gt;L) and 3161C&gt;G (1054P&gt;R) variants had a higher level of MN after IR exposure compared to that observed in the remaining four BC or in the normal cell lines. This increase was not related to the constitutive <jats:italic>ATM<\/jats:italic> mRNA level, which was similar in these BC and the normal cell lines. Our results indicate that alterations in the <jats:italic>ATM<\/jats:italic> gene, including the presence of heterozygous mutations and the 2572C and 3161G variant alleles, are associated with increased in vitro chromosomal radiosensitivity, perhaps by interfering with <jats:italic>ATM<\/jats:italic> function in a dominant\u2010negative manner. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20025","type":"journal-article","created":{"date-parts":[[2004,3,26]],"date-time":"2004-03-26T21:02:26Z","timestamp":1080334946000},"page":"109-119","source":"Crossref","is-referenced-by-count":72,"title":["Functional consequences of <i>ATM<\/i> sequence variants for chromosomal 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