Disease relevance of Retronecine pyrrole

• Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized [1].
• In order to examine the relationship between DNA adduct levels and the incidence of hemangiosarcomas, we have measured DHR-derived DNA adduct levels in purified rat and mouse liver endothelial cells, the cells of origin for the hemangiosarcomas [2].
• Four-month-old rhesus monkeys were injected with 65 mg of [3H] dehydroretronecine per kg body weight and sacrificed at 6,12 and 24 h following injection [3].

High impact information on Retronecine pyrrole

• Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year [1].
• Alkylation of N2 in deoxyguanosine by dehydroretronecine, a carcinogenic metabolite of the pyrrolizidine alkaloid monocrotaline [4].
• The effect of a pyrrolizidine alkaloid, monocrotaline, and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium [5].
• Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites [6].
• First, the metabolic activation to produce the toxic pyrrolic ester followed by formations of bound pyrroles, dehydroretronecine, 7-glutathionyldehydroretronecine, and clivoric acid were found in female rats, and CYP3A1/2 isozymes were identified to catalyze the metabolic activation [7].

Biological context of Retronecine pyrrole

• Tissue distribution, binding properties and lesions produced by dehydroretronecine in the nonhuman primate [3].

Anatomical context of Retronecine pyrrole

• The metabolite, dehydroretronecine, which had previously been isolated from rat hepatic microsomes, was not detected, and minor metabolites were not identified [8].
• The DHR-derived DNA adduct levels in the endothelial cells were significantly greater than in the parenchymal cells [2].
• Likewise, it was in the gastric mucosa that the lesions produced by dehydroretronecine were the most severe [3].
• Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions [9].

Associations of Retronecine pyrrole with other chemical compounds

• The metabolite dehydroretronecine which had previously been isolated from rat hepatic microsomes, was not detected while senecic acid, 19-hydroxysenecionine, and senecionine N-oxide were again present [10].

Gene context of Retronecine pyrrole

• 5. The mass spectrum of this DHP-GSH conjugate was identical to that of the chemically-synthesized dehydroretronecine (the R enantiomer of the racemic DHP) and GSH [11].
• Inhibition of yeast alcohol dehydrogenase by dehydroretronecine [12].

Analytical, diagnostic and therapeutic context of Retronecine pyrrole

• Development of a (32)P-postlabeling/HPLC method for detection of dehydroretronecine-derived DNA adducts in vivo and in vitro [13].
• The perfusion medium at the end of the perfusion contained 113 nmol/g liver of the two pyrroles, dehydroretronecine and glutathionyldehydroretronecine [14].

References