title: Tumor-promoting activity of p-hydroxybenzenediazonium is accelerated in Mg-deficient rats.
abstract: Tumor-promoting activity caused by the short-term administration of p-hydroxybenzenediazonium (PDQ) has been assayed in rats fed on a Mg-deficient diet as a reference model versus rats fed on a standard diet as controls. For 5 weeks groups of 20 rats, fed either on the Mg-deficient or standard diet, were treated simultaneously with PDQ. A group of 10 Mg-deficient rats remained untreated. Topical application of PDQ was followed by the appearance of macroscopic alterations in the skin, which were more evident in the Mg-deficient rats. No deaths occurred during the treatment. After 5 weeks' PDQ treatment the rats were killed and histological analyses were made. Tissues from the skin, liver, heart, kidney, lung and thymus were screened by conventional staining methods. Both the PDQ-treated Mg-deficient and PDQ-treated control rats presented tissue lesions, although to a different extent. The untreated Mg-deficient rats showed no such lesions. Mg-deficient rats treated with PDQ developed significant incipient fibrosarcomas (p<0.05) and extended hyperplasia (p<0.001), particularly in the skin, accompanied by a significant increase in the thickness of collagen (mean value: 445.4+/-47.2microm, p<0.05) compared to the control PDQ-treated group (mean values: 258.7+/-36.4microm). The overall results provide objective proof of tumor-promoting activity after 5 weeks' treatment with PDQ. Such a fast response is interpreted as being linked to the increased vulnerability of the membrane caused by Mg deficiency, which would more readily facilitate the toxic activity of p-hydroxybenzenediazonium ions.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain. bqosso@ugr.es
authors.forename: Bartolome
authors.initials: B
authors.lastname: Quintero
authors.forename: Elena
authors.initials: E
authors.lastname: Planells
authors.forename: María
authors.initials: M
authors.lastname: del Carmen Cabeza
authors.forename: Javier
authors.initials: J
authors.lastname: Esquivias
authors.forename: María
authors.initials: M
authors.lastname: del Pilar Gutiérrez
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez
authors.forename: Pilar
authors.initials: P
authors.lastname: Aranda
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Juan
authors.initials: J
authors.lastname: Llopis
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003979:Diazonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis
chemical_list: D003979:Diazonium Compounds; C508525:p-hydroxybenzenediazonium