title: DNA fragmentation and DNA repair synthesis induced in rat and human thyroid cells by chemicals carcinogenic to the rat thyroid.
abstract: Five chemicals that are known to induce in rats thyroid follicular-cell adenomas and carcinomas were assayed for their ability to induce DNA damage and DNA repair synthesis in primary cultures of human thyroid cells. Significant dose-dependent increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measured by the same Comet assay, were obtained after a 20-h exposure to the following subtoxic concentrations of the five test compounds: methimazole from 2.5 to 10mM; nitrobenzene, potassium bromate, N,N'-diethylthiourea and ethylenethiourea from 1.25 to 5mM. Under the same experimental conditions, DNA repair synthesis, as evaluated by quantitative autoradiography, was present in potassium bromate-exposed thyroid cells from all the three donors and in those from two of three donors with either nitrobenzene or ethylenethiourea, but did not match the criteria for a positive response in thyroid cells from any of the donors with methimazole and N,N'-diethylthiourea. Consistently with their ability to induce thyroid tumors, all the five test compounds, administered p.o. in rats in a single dose corresponding to 1/2 LD50, induced a statistically significant degree of DNA fragmentation in the thyroid. These findings suggest that the five test compounds might be carcinogenic to thyroid in humans.
authors.affiliation: Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV, 2, I-16132 Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mattioli
authors.forename: Antonietta
authors.initials: A
authors.lastname: Martelli
authors.forename: Marzia
authors.initials: M
authors.lastname: Gosmar
authors.forename: Claudia
authors.initials: C
authors.lastname: Garbero
authors.forename: Valeria
authors.initials: V
authors.lastname: Manfredi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Varaldo
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Torre
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brambilla
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001959:Bromates / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D005031:Ethylenethiourea / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008713:Methimazole / Q000633:toxicity; D009578:Nitrobenzenes / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000633:toxicity; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000139:chemically induced
chemical_list: D001959:Bromates; D002273:Carcinogens; D009578:Nitrobenzenes; C019536:potassium bromate; D005031:Ethylenethiourea; C035318:diethylthiourea; D008713:Methimazole; C036077:nitrobenzene; D013890:Thiourea