Disease relevance of Lethal Dose 50

• Female C57BL/Cbl mice were treated with single ip doses of HNU to determine its median lethal dose (LD50) and its ability to induce lymphocytic thymic lymphomas in these mice [1].
• Fully susceptible BALB/cJ mice, infected with 100 50% lethal doses (LD50) of MHV-3 developed histologic and biochemical evidence of fulminant hepatitis, as evidenced by massive hepatic necrosis with hypoglycemia, metabolic acidosis, and a markedly elevated serum alanine aminotransferase (ALT) (mean, 1,402 +/- 619 IU/liter) [2].
• Bone marrow cells had a toxicity profile similar to that of FUra (LD50 = 10 microM) but were relatively insensitive to FUH2 (LD50 greater than 250 microM), with no sensitivity to alpha-fluoro-beta-alanine [3].
• Ehrlich ascites tumor cells were more sensitive to FUra [50% lethal dose (LD50) = 18 microM] than to FUH2 [LD50 = 50 microM], with no sensitivity to alpha-fluoro-beta-alanine even at 250 microM [3].
• 5'-dFUrd was less potent than was 5-fluorouracil or 5-fluoro-2'-deoxyuridine in all cells examined, exhibiting its best activity against the 47-DN [concentration that prevented 50% clonal growth compared to untreated control (LD50) = 32 microM] and MCF-7 (LD50 = 35 microM) breast carcinomas and MG-63 osteosarcoma (LD50 = 41 microM) [4].

Psychiatry related information on Lethal Dose 50

• Mice intravenously injected with concentrated infectious influenza B/Lee/40 virus (LD50 = 6400 hemagglutinin units) developed lethargy, seizures, coma, and death 1 to 3 days later [5].
• Conversely, if levels of cerebral prostaglandins were enhanced by a preceding electroshock, the toxicity of pentylenetetrazole was significantly reduced (increase in LD50), and the time of onset of clonic seizures was markedly prolonged [6].
• The induction of MN was significantly higher in foetal than adult cells for 0.75 LD50 monocrotaline and benzidine after 21 h (p < 0.0005), and for one LD50 heliotrine at 12, 24 and 30 h after injection in a time-response study (p < 0.02) [7].
• Pathogen-free OF1 male and female mice of six different ages (between 31 and 387 days), grouped by 10, sex-separated and synchronized by a light (100 lux)-dark 12:12 alternation, were submitted to an acute LD50 carbon monoxide intoxication during the light period during which respiratory and motor activities are at a minimum [8].
• Soman (less than or equal to 3% LD50), physostigmine (less than or equal to 4.5% LD50), and pyridostigmine (less than or equal to 10% LD50) interfered with two-way shuttlebox avoidance learning, open field behavior, and complex coordinated movements ( hurdle -stepping task) [9].

High impact information on Lethal Dose 50

• Injected PON1 protects against OP poisoning in rodent model systems and interspecies differences in PON1 activity correlate well with observed median lethal dose (LD50) values [10].
• To determine whether alcohol enhances acetaminophen hepatotoxicity, a lethal dose for 50% survival of a test group (LD50) was performed for mice fed 10% alcohol in their water supply for three weeks and for mice receiving a normal diet only [11].
• The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude [12].
• In adult HA/ICR mice pretreated with ferric chloride, the LD50 for S-plus strain 84-32 was 43.3 times lower than its spontaneous S-minus mutant 84-54 [13].
• Incubation of cells with 200 microM zinc acetate before exposure to copper, raised the LD50 for confluent cells to 1,250 microM copper chloride, improved protein synthesis, and increased synthesis of a 10-kD protein, apparently metallothionein [14].

Chemical compound and disease context of Lethal Dose 50

• Nimodipine, an antagonist of voltage-sensitive calcium channels, protected cells against cadmium toxicity by increasing the LD50 for CdCl2 from 15 to 45 microM, whereas the calcium channel agonist BAY K8644 decreased the LD50 [15].
• Toxicity assays in vivo established that sP05-NH2, like native P05, is a potent and lethal neurotoxic agent in mice (LD50 of 20 ng per mouse) [16].
• Liposome-encapsulated MTP-PE (L-MTP-PE) was superior to free MTP-PE in activating alveolar macrophages and in protecting mice against intranasal challenge with 10 LD50 (50% lethal dose) of herpes simplex virus type 1 (HSV-1) [17].
• Six additional serotypes (K12, K24, K32, K55, K62, and K67) were examined, and all showed a positive correlation between the ability of the Klebsiella serotype to interact with a human mannose receptor, as expressed by Cos I cell recombinants, and the LD50 of the serotype [18].
• Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli [19].

Biological context of Lethal Dose 50

• At the same time, cell viability was determined by trypan blue exclusion and revealed median lethal doses (LD50) of 3.5 micrograms/ml (HL60), 15 micrograms/ml (Raji), 24 micrograms/ml (L1210), and 38 micrograms/ml (K562) [20].
• Median lethal doses (LD50) for PMB-decaprenylamine and SDB-ethylenediamine administered ip were 123 and 350 mg/kg against mice, whereas the LD50 for verapamil, another modifier of cellular drug resistance, was about 7.6 mg/kg [21].
• Exposure of septohippocampal cultures to 1.0, 2.0, and 4.0 mmol/L glutamate induced a dose-dependent cell death with an LD50 of 2.0 mmol/L glutamate after 24 hours of incubation [22].
• Virulence plasmids, which are found in a small number of Salmonella serotypes, greatly enhance the extraintestinal growth of salmonellae and lower the LD50 by 2-5 logs in experimental murine infections [23].
• In contrast, an S. typhimurium strain carrying mutations in all four fimbrial operons (quadruple mutant) had a 26-fold increased oral LD50 [24].

Anatomical context of Lethal Dose 50

• A sublethal dose of 100 mg lucanthone hydrochioride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters [median lethal dose for 30-day survival (LD50/30) of 315 mg/kg] reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow [25].
• A direct relationship (r = 0.78) of paraquat LD50 and CuZnSOD activity was also observed with a panel of six lines of SOD1- transfected HeLa cells with 1.6- to 7.3-fold the basal CuZnSOD activity [26].
• We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms) [27].
• However, these cancer cells showed sensitivity to flavopiridol with an average LD50 of 50 nmol/L (range, 21.5-69 nmol/L), similar to the LD50 in established cell lines [28].
• In the CLB-resistant CLL lymphocytes, there was a linear correlation between induction of Rad51 protein at 5.4 microM CLB and the in vitro LD50 dose of CLB [29].

Associations of Lethal Dose 50 with chemical compounds

• The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation [25].
• The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively [25].
• Heat fractionation with gentamicin increased the LD50/7 (total time at 45 degrees C) to 23.0 and 12.5 minutes at 45 degrees C for 1- and 3-day intervals, respectively [30].
• The results showed that the LD50 was the same as that for 1-ethyl-1-nitrosourea (ENU) and that its was slightly more potent than ENU as a carcinogen in this system [1].
• Animals were divided into 3 groups: Group I received ip injections of freshly prepared senkirkine at a dose of 10% of the median lethal dose (LD50) twice weekly for 4 weeks and then once a week for 52 weeks [31].

Gene context of Lethal Dose 50

• In vivo studies revealed that Mut2 was more effective than TNF or LT against MethA (a mouse tumor line) as judged by the therapeutic ratio [calculated as LD50 (dose that kills 50% of the animals)/ED50 (dose that reduces the tumor size by 50%)] [32].
• First, deletion of the gene encoding the calcineurin regulatory B subunit, CNB1, from a wild-type strain decreases the LD50 of alpha-factor but has no further effect on a cmd1-6 strain [33].
• Deletion of the CMK1 and CMK2 genes, which encode CaMK, decreases the LD50 of pheromone compared with that for a wild-type strain but again has no effect in a cmd1-6 strain [33].
• The LD50 for the mouse of the yscH mutant was 10-fold higher than that of the parental strain indicating that YopR is involved in pathogenesis [34].
• The LD50 was not affected by rhIL-11 but was 10-fold lower in the anti-TNF MAb group (P<.001) [35].

Analytical, diagnostic and therapeutic context of Lethal Dose 50

• Group II received ip injections of symphytine at a dose of 10% of the LD50 by the same injection schedule as in group I. The control group was given ip injections of a 0.9% NaCl solution following the same injection schedule as in experimental groups [31].
• Effects of intraventricular injection of sheep anti-somatostatin gamma-globulin (anti-SSG) on strychnine-induced seizures, strychnine LD50, and pentobarbital LD50 were examined in male rats under light ether anesthesia [36].
• After an intraperitoneal injection of an LD50 dose of endotoxin, the activity of the sinusoidal acid phosphatase isozyme reached a maximum at 1 hour, and was followed by an elevation of the activity of the isozymes derived from parenchymal cells [37].
• The LD50 and the nonfetolethal maximum dosage of DEHP in its single, oral administration was 592 mg/kg and 64 mg/kg, respectively [38].
• In an animal model used to assess the effect of cimetidine on acetaminophen toxicity, the LD50 of acetaminophen alone in Charles River CD-1 mice was 480 mg/kg (95% confidence interval: 436-528 mg/kg) [39].

References