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To begin to test this hypothesis, we utilized a mouse model (NIH Swiss) in which exposure of fathers to Cr(III) chloride 2 wk before mating can alter incidence of neoplastic and nonneoplastic changes in offspring tissues. Utilizing a MS\u2010RDA approach, we found that the sperm of these fathers had a significantly higher percentage of undermethylated copies of the <jats:italic>45S<\/jats:italic> ribosomal RNA gene (<jats:italic>rRNA<\/jats:italic>); this finding was confirmed by bisulfite sequencing. Because gene methylation is a known mechanism of expression control in germ cells, and ribosomal RNA levels have been linked to cancer, these findings are consistent with the hypothesis. Secondly, we observed that offspring of Cr(III)\u2010treated fathers were significantly heavier than controls, and had higher levels of serum T3. Possible effects of T3 levels on gene expression in the offspring were examined by microarray analysis of cDNAs from liver. A total of 58 genes, including 25 named genes, had expression ratios that correlated significantly with serum T3 ratios at <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.001. Some of these genes have potential roles in growth and\/or tumor suppression. These results also support the hypothesis of an epigenetic and\/or gene expression\u2013based mechanism for transgenerational carcinogenesis. Published 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20022","type":"journal-article","created":{"date-parts":[[2004,4,20]],"date-time":"2004-04-20T07:01:19Z","timestamp":1082444479000},"page":"1-11","source":"Crossref","is-referenced-by-count":65,"title":["Epigenetic and gene expression changes related to transgenerational carcinogenesis"],"prefix":"10.1002","volume":"40","author":[{"given":"Robert Y\u2010S.","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Hockman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy 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