{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T07:38:14Z","timestamp":1773733094952,"version":"3.50.1"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,5,19]],"date-time":"2005-05-19T00:00:00Z","timestamp":1116460800000},"content-version":"vor","delay-in-days":7901,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratology"],"published-print":{"date-parts":[[1983,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A previous study demonstrated that caffeine strongly potentiated the teratogenic action of mitomycin C in mice. In the present study the effect of methylxanthines including caffeine, theophylline, theobromine (theobromine sodium salicylate), paraxanthine, and 1\u2010methylxanthine was compared in order to analyze the structure\u2010activity relationship. Jcl:ICR mice were injected IP with 3 mg\/kg of mitomycin C, immediately followed by SC injection of each methylxanthine on day 11 of gestation. The doses of methylxanthines were calculated so that the mice received 50 mg\/kg of caffeine or the equimolecular amount of the other methylxanthines. Fetuses were examined for external malformations on day 18 of gestation.<\/jats:p><jats:p>Mitomycin C at 3 mg\/kg and the methylxanthines at the doses used were not teratogenic. Combined administration of caffeine or theophylline with mitomycin C produced more than 80% of malformed fetuses. Although less effective than caffeine or theophylline, paraxanthine also significantly increased the incidence of malformed fetuses. Theobromine and 1\u2010methylxanthine were virtually ineffective. From these findings, it is suggested that the methyl group at N\u20101 position of the xanthines is important for the enhancement but the N\u20101 methylation alone is ineffective unless accompanied with the substitution of the methyl moiety at the other position(s).<\/jats:p>","DOI":"10.1002\/tera.1420280214","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T14:45:23Z","timestamp":1118501123000},"page":"243-247","source":"Crossref","is-referenced-by-count":15,"title":["Potentiating effects of methylxanthines on teratogenicity of mitomycin C in mice"],"prefix":"10.1002","volume":"28","author":[{"given":"Toshio","family":"Nakatsuka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Hanada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,5,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1981.98"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(81)90062-2"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.2535\/ofaj1936.46.4_167"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420280106"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553007814550401"},{"key":"e_1_2_1_7_1","volume-title":"Caffeine and Chromosomes","author":"Kihlman B. A.","year":"1977"},{"key":"e_1_2_1_8_1","first-page":"592","volume-title":"The Pharmacological Basis of Therapeutics","author":"Rall T. W.","year":"1980"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.2307\/3572165"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(18)31162-X"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.2535\/ofaj1936.44.4_203"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(77)90016-1"},{"key":"e_1_2_1_13_1","volume-title":"Some Rapid Approximate Statistical Procedure","author":"Wilcoxon F.","year":"1965"}],"container-title":["Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Ftera.1420280214","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tera.1420280214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T08:42:16Z","timestamp":1697791336000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tera.1420280214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1983,10]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1983,10]]}},"alternative-id":["10.1002\/tera.1420280214"],"URL":"https:\/\/doi.org\/10.1002\/tera.1420280214","archive":["Portico"],"relation":{},"ISSN":["0040-3709","1096-9926"],"issn-type":[{"value":"0040-3709","type":"print"},{"value":"1096-9926","type":"electronic"}],"subject":[],"published":{"date-parts":[[1983,10]]}}}