Disease relevance of hycanthone

• A follow-up liver biopsy in a 4th patient who had had hycanthone hepatitis with liver failure 1 year before showed good recovery with features of chronic persistent hepatitis [1].
• In infected mice, the overall incidence of hepatomas and hepatocellular carcinomas increased from 3.4% in untreated mice to 10.6% in those treated with hycanthone [2].
• Seven percent of hycanthone-treated patients demonstrated hepatic toxicity which was usually mild in nature [3].
• Evaluation of external-beam radiation therapy plus 5-fluorouracil (5-FU) versus external-beam radiation therapy plus hycanthone (HYC) in confined, unresectable pancreatic cancer [3].
• Hycanthone dose-response in treatment of schistosomiasis mansoni in St. Lucia [4].

Psychiatry related information on hycanthone

• The effect of the antischistosomal drug hycanthone on the motor activity of Schistosoma mansoni was studied in vitro [5].

High impact information on hycanthone

• Early steps in mutagenesis by hycanthone [6].
• Induction of DNA repair synthesis could not be detected by autoradiography after exposure of cells to hycanthone [6].
• Hycanthone, the most potent mutagen in a series of nine thiaxanthenones, is a potent inducer of nuclear immunoreactivity to antinucleoside antibodies in HeLa cells [6].
• Unlike those of many other mutagens, the metabolic effects and immunoreactivity induction of hycanthone were readily reversible [6].
• Immunoreactivity to antinucleoside antibodies was also induced by brief exposure to hycanthone, 3 microgram/ml, in human fibroblasts from three normal subjects and in fibroblasts from seven patients with DNA repair deficiencies [6].

Chemical compound and disease context of hycanthone

• The treatment of schistosomiasis mansoni in Murang'a District, Kenya: a double blind controlled trial of three hycanthone regimens and oxamniquine [7].
• During the pase 24 years, several million patients with schistosomiasis have been treated with lucanthone, and in recent years about 700 000 persons with hycanthone [8].
• Mice infected with these strains were treated 45 days later with niridazole (50 or 100 mg/kg body weight per day for 5 days, per os), hycanthone (single dose of 80 or 160 mg/kg, intramuscularly), or oxamniquine (single dose of 50 or 100 mg/kg, per os) [9].

Biological context of hycanthone

• DNAase I footprinting has been used to probe the DNA sequence selectivity of the antitumor intercalating agents lucanthone (1), hycanthone (2), 6-chlorolucanthone (7), and four indazole analogs (IA-3-IA-6) [10].
• Hycanthone was administered to Schistosoma mansoni-infected and non-infected Syrian golden hamsters and Swiss mice by intraperitoneal and intramuscular injection of amounts up to the maximum tolerated dose [2].
• In this report, hycanthone is shown to be weakly active in inducing ring-X chromosome loss [11].
• Ribosomal gene probes were used to investigate the genetic basis of drug resistance in schistosomes in a model where resistance to the anthelmintic hycanthone (HC) is generated by exposing immature worms to the drug [12].
• These results strongly support a previously proposed mechanism of action of hycanthone, which is based essentially on the alkylation of worm macromolecules by a drug derivative produced in sensitive schistosomes [13].

Anatomical context of hycanthone

• Treatment with mitomycin C (0.05 micrograms/ml), hycanthone (0.1 micrograms/ml) and gamma-radiation (0.1 Gy) revealed a significant (P less than 0.01) increase in frequencies of SCE in DS lymphocytes and in those of their parents as compared to controls [14].
• Hydroxymethyl analogues, including hycathone (Etrenol), are mutagenic in the absence of microsomes [8].
• (1) A refined brood-pattern analysis of hycanthone-induced sex-linked recessive lethals confirmed the specific sensitivity of mid- and late spermatids [11].
• The effects of the antischistosomal drug, hycanthone, on the synaptic transmission at the frog neuromuscular junction were studied [15].
• A mouse was considered to harbor resistant schistosomes if, three weeks or more after a single intrasmuscular injection of 80 mg/kg hycanthone schistosome eggs were still excreted in the feces, at least one normal worm pair was obtained by perfusion, or miracidia could be seen hatching from the liver [16].

Associations of hycanthone with other chemical compounds

• Acetylcholine receptors in Schistosoma Mansoni: visualization and blockade by hycanthone [17].
• Caffeine interactions with methyl methanesulphonate, hycanthone, benlate, and cadmium chloride in chromosomal meiotic segregation of Saccharomyces cerevisiae [18].
• Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazenes, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome breakage were the only indicator for mutagenic activity [19].
• The hycanthone-induced inhibition of uridine incorporation was essentially irreversible upon removal of the drug in adult schistosomes, while it was completely reversible in hycanthone-resistant worms, in immature worms and in HeLa cells [20].
• The greatest effects were found on the induction of diploid spores: MMS, hycanthone, and distamycin demonstrated strong, benlate little synergistic action [18].

Gene context of hycanthone

• These findings are in contrast to a recent report of very considerable increases in content or in 5HT acquisition in vitro by hycanthone-exposed parasites [21].
• Hycanthone is an inhibitor of acetylcholinesterase (ACHE) from S. mansoni, but is less effective against ACHE of mammalian origin [5].
• Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo [22].
• Liver and bladder tissues of these animals exhibited a pattern of alteration in the MGMT activity similar to that observed for hycanthone [23].
• Case report: Severe jaundice following hycanthone [24].

Analytical, diagnostic and therapeutic context of hycanthone

• The antimuscarinic activity of hycanthone and five antischistosomal analogs was determined in three biological assays of cholinergic systems [25].
• Hycanthone-resistant schistosomes, when tested between 1 and 7 days after treatment, showed a pattern of precursor incorporation which was virtually identical to that of untreated worms [26].
• Schistosomes obtained by perfusion from host animals as early as 2 hours after in vivo treatment with hycanthone and transferred into untreated recipient hamsters died in the recipient host [27].
• Plasma and tissue concentrations of hycanthone in the mouse determined by reversed-phase high-performance liquid chromatography [28].
• Clinical trials of hycanthone (single intramuscular dose) were undertaken in schistosomiasis mansoni patients in St [4].

References