{"doi":"10.1002/tera.1420280214","title":"Potentiating effects of methylxanthines on teratogenicity of mitomycin C in mice","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‐methylxanthine was compared in order to analyze the structure‐activity 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‐methylxanthine were virtually ineffective. From these findings, it is suggested that the methyl group at N‐1 position of the xanthines is important for the enhancement but the N‐1 methylation alone is ineffective unless accompanied with the substitution of the methyl moiety at the other position(s).</jats:p>","journal":"Teratology","year":1983,"id":26745,"datarank":1.4009142242577035,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.9850259159217363,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.9850259159217363,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":15,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":154031,"name":"Satoshi Hanada","orcid":null,"position":1,"is_corresponding":false},{"id":154032,"name":"Takaaki Fujii","orcid":null,"position":2,"is_corresponding":false},{"id":154030,"name":"Toshio Nakatsuka","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"6417813","pmcid":null,"openalex_id":"https://openalex.org/W2063968999","authors":[],"funders":[],"total_grants":0,"fwci":0.2972,"citation_percentile":0.56798457,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2017,"count":1},{"year":2023,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Ftera.1420280214","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/tera.1420280214","host_type":"publisher"},{"url":"https://doi.org/10.1002/tera.1420280214","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/6417813","host_type":"repository"}],"fields_of_study":["Reproductive System and Pregnancy","Breastfeeding Practices and Influences","DNA and Nucleic Acid Chemistry","Chemistry","Medicine","Abnormalities, Drug-Induced","Animals","Antibiotics, Antineoplastic","Caffeine","Drug Synergism","Female","Mice","Mice, Inbred ICR","Mitomycin","Mitomycins","Pregnancy","Structure-Activity Relationship","Theobromine","Theophylline","Xanthines"],"mesh_terms":["Abnormalities, Drug-Induced","Animals","Antibiotics, Antineoplastic","Caffeine","Drug Synergism","Female","Mice, Inbred ICR","Mitomycins","Pregnancy","Structure-Activity Relationship","Theobromine","Theophylline","Xanthines","Mitomycin","Mice"],"keywords":["Theobromine","Theophylline","Caffeine","Paraxanthine","Chemistry","Pharmacology","Mitomycin C","Aminophylline","Endocrinology","Biochemistry","Medicine","Metabolism","Surgery"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T15:34:42.144727Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}