{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:56:10Z","timestamp":1770432970320,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":5314,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1992,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>O<\/jats:italic><jats:sup>6<\/jats:sup>\u2010Alkylguanine\u2010DNA alkyltransferase (ATase) activity was determined in crude sonicates of tissues obtained from the F2 offspring of human ATase transgenic founder mice. In certain cases, samples were analyzed both before and after administration of zinc sulfate in the drinking water for 2 wk to upregulate the mouse metallothionein\u20101 promoter that controls the expression of the transgene. In liver samples obtained by partial hepatectomy, the ATase activities of nontransgenic mice ranged from 63 to 139 fmol\/mg total protein (mean of 10 mice, 95.3 \u00b1 23 fmol\/mg), whereas in positive transgenic mice, the range was from 503 to 2119 fmol\/mg (mean of 10 mice, 963 \u00b1 475 fmol\/mg). The difference between the mean ATase values for these two groups of mice is highly significant (<jats:italic>P<\/jats:italic> &lt; 0.001). All positive mice expressed ATase and in those examined using the human ATase coding sequence as a probe, isoschizomeric\u2010restriction endonuclease digestion showed no evidence of cytosine methylation in the transgene. After zinc sulfate induction, the ATase levels in residual liver tissue were for the controls 84\u2013191 fmol\/mg (mean of 10 mice, 123 \u00b1 31.5 fmol\/mg) and for positive mice 908\u20133273 fmol\/mg (mean of 10 mice, 1960 \u00b1 724 fmol\/mg). Induction thus caused a 1.4\u2010 to 3.2\u2010fold increase in ATase activity in the tissues of individual transgenic mice (mean, 1.8\u2010fold; <jats:italic>P<\/jats:italic> &lt; 0.003), with the greatest increase generally occurring in those mice that had the lowest preinduction levels. Hepatic ATase levels were thus increased up to 28 times higher in transgenic mice than in nontransgenic mice. When data from other groups of transgenic and nontransgenic mice (eight of each) was included and analyzed in an independent rather than paired fashion, the mean values for zinc\u2010treated controls and transgenic mice, respectively, were 106 fmol\/mg and 1415 fmol\/mg, still a highly significant (<jats:italic>P<\/jats:italic> &lt; 0.001) difference. In two mice given a single intraperitoneal dose of cadmium chloride, hepatic ATase increased 2.1\u2010 and 4.9\u2010fold, respectively. The effect of partial hepatectomy alone was also considered: for transgenic mice the mean ATase level increased from 453 to 661 fmol\/mg protein after 48 h. In other offspring subjected to either unilateral nephrectomy or orchidectomy, induction of ATase activity by zinc sulfate was also seen in kidney (5.7\u2010 and 8.4\u2010fold) and testis (1.7\u2010 and 3.1\u2010fold), although these observations were made with small numbers of mice. Northern and slot\u2010blot analyses showed that the induction of ATase activity in liver and testis was accompanied by increases in the abundance of human ATase message in total RNA, but there was not a close correlation. In a follow\u2010up experiment, a comparison of ATase levels in zinc\u2010induced transgenic tissues with tissue from nontransgenic littermates (eight of each) showed a statistically significant enhancement of human ATase expression in transgenic kidney and testis as well as in brain, stomach, spleen, and thymus. Lung was the only tissue analyzed that did not show expression of the transgene. The small intestine in particular was shown to have ATase levels ranging from 1086 to 2097 fmol\/mg (greater than 16 times normal mouse levels). In xeroderma pigmentosum fibroblasts transfected with the human ATase metallothionein chimeric vector and exposed to zinc sulfate in the culture medium (100 mM), ATase expression was increased somewhat more than in transgenic liver (i.e., 4.4\u2010fold). \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.2940060106","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:11:34Z","timestamp":1172088694000},"page":"26-31","source":"Crossref","is-referenced-by-count":5,"title":["Tissue\u2010specific expression and induction of human <i>O<\/i><sup>6<\/sup>\u2010alkylguanine\u2010dna alkyltransferase in transgenic mice"],"prefix":"10.1002","volume":"6","author":[{"given":"Joseph A.","family":"Rafferty","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun\u2010Yang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip 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