LD50 Assay Research Articles

Toxicity, Radiation Sensitivity Modification, and Combined Drug Effects of Ascorbic Acid With Misonidazole In Vivo on FSall Murine Fibrosarcomas<xref ref-type="fn" rid="FN2">2</xref>

Ascorbic acid (ASC) has been shown to radioprotect nonmalignant tissue and to enhance the effects of misonidazole (MISO) on hypoxic cells in vitro. Since ASC is minimally toxic, it is an interesting candidate for improving the radiotherapeutic gain factor in vivo. The in vivo radiomodifying effects of ASC on a C3H/fSed murine fibrosarcoma (FSaII), on normal skin, and on bone marrow were determined with the use of the tumor growth delay and TCD50 (i.e., radiation dose required to control 50% of treated tumors for a minimum of 120 days) assays and the RD50 (i.e., dose required to cause a peak skin reaction of 2 in 50% of treated hind limbs) and LD50 (i.e., whole-body radiation lethal dose) assays, respectively. ASC was buffered to pH 7.35 and delivered ip at a dose of 4.5 mg g-1 body weight. ASC did not modify tumor growth delay induced by radiation or the TCD50 [87.1 Gy (control) vs. 85.6 Gy (ASC)]. Normal tissues, however, were radioprotected by ASC. RD50 values for 2+ acute skin reactions were 46.4 and 55.7 Gy for control and ASC-treated subjects, respectively; LD50 (30 days) values were 7.2 and 8.5 Gy. The enhancement ratios for skin and bone marrow were 1.20 and 1.18, and 95% confidence limits were (1.07 ... 1.34) and (1.14 ... 1.23), respectively. The therapeutic gain factor was 1.22 calculated as the ratio of the TCD50 and the reference normal tissue (RD50 or LD50). When ASC and MISO were combined, ASC reduced the in vivo radiosensitizing effects of MISO.

The value of combining the radiosensitizer misonidazole with cyclophosphamide in treating the murine Lewis lung tumor

Cyclophosphamide and the radiosensitizer misonidazole were combined to determine if any therapeutic benefit could be demonstrated with this combination in treating the murine Lewis lung tumor. The results of our in vivo studies indicated that when various dosage schedules of misonidazole were combined with cyclophosphamide, the tumor effect was greater than when cyclophosphamide was administered alone. However, the increased effect of the two drug combination was determined to be no greater than an additive effect of cyclophosphamide tumor cell toxicity plus misonidazole cytotoxicity. Furthermore, host toxicity was enhanced when the two drugs were combined as indicated by the LD50 assay. We conclude that combining cyclophosphamide with misonidazole offers little if any therapeutic advantage since the increase in host toxicity appears to be as great as the increase in tumor cell killing.

ChemInform Abstract: DIELS‐ALDER ADDUCTS OF FULVENES AND HALOGENATED DIENES. SYNTHESIS AND INSECTICIDAL ACTIVITY

AbstractDurch eine Cycloaddition von disubstituierten Fulvenen mit polyhalogenierten Cyclopentadienen erhält man die endo‐Verbindungen (I).

Diels-Alder adducts of fulvenes and halogenated dienes. Synthesis and insecticidal activity.

A series of eight adducts (1--8) of substituted fulvenes and polychlorinated cyclodienes was synthesized by Diels-Alder cyclization. The products isolated were the endo bicyclo adducts as determined by detailed 1H and 13C NMR spectral analysis. Steric hindrance of end-product bridge substituents coupled with bulky substituents at C6 of the fulvenes led to one isomeric product in most cases. Compounds 1--8 demonstrated weak insecticidal action in Musca domestica as determined by topical LD50 and oral LC50 assays.

An improved method for titration of mouse hepatitis virus type 3 in a mouse cell culture

SummaryPlaque assay in DBT cells with DEAE-dextran and trypsin presents a titration system for MHV3 as sensitive as the LD50 assay in mice.