Detail of "15475-56-6"

Reference

Drug-induced limb dysplasias in fetal rabbits

Drug-induced limb dysplasias in fetal rabbits. DeSesso, John M.; Jordan, Robert L. (Dep. Anat., Virginia Commonw. Univ., Richmond, Va., USA). Teratology, 15(2), 199-204 (English) 1977. CODEN: TJADAB. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Pregnant New Zealand White rabbits were treated on gestation day 12 with methotrexate Na (MTX) [15475-56-6] (19.2 mg/kg), hydroxyurea (HU) [127-07-1] (750 mg/kg), or acetazolamide Na [1424-27-7] (1500 mg/kg). Rabbits were killed either 2-32 h posttreatment for histol. anal. of embryos or at day 29 for gross and skeletal examn. of fetuses. MTX produced cleft palate, hydrocephalus, and fore- and hindlimb redn. defects. Histol. anal. revealed pyknosis and edema in mesenchymal tissues at 4-8 h following treatment. The apical ectodermal ridges (AER) of treated embryos permanently lost their characteristic pseudostratified organization. By 32 h the limb buds had regained their normal appearance except for the AER. HU affected all fetuses with skull and facial anomalies as well as severe redn. deformities of all limbs. Histol. HU-treated embryos had numerous, basophilic, intercellular granules (presumably cell debris) which appeared within 2-4 h in the limb bud mesenchyme, neural tube, and dorsal root ganglion. The architecture of the AER was unchanged. Acetazolamide produced bilateral retarded ossification or possible aplasia of the 1st metacarpal and talus in nearly 80% of fetuses. Microscopic examn. disclosed no apparent alterations in limb-bud morphol. Methyl green-pyronin Y staining called attention to green intracellular droplets within endoderm of the trachea and bronchi at 2 h posttreatment. Thus, the 3 drugs do not produce limb dysplasias by a common teratogenic mechanism.

Combined therapy of the spontaneous mouse mammary tumor: methotrexate and hyperbaric oxygen irradiation

Combined therapy of the spontaneous mouse mammary tumor: methotrexate and hyperbaric oxygen irradiation. Shewell, Jennifer; Davies, R. W. (Dep. Radiobiol., Med. Coll. St. Bartholomew's Hosp., London, Engl.). Eur. J. Cancer, 13(9), 977-84 (English) 1977. CODEN: EJCAAH. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) Section cross-reference(s): 8 The response of spontaneous mammary adenocarcinoma of mice to combinations of methotrexate Na (I Na) [15475-56-6] administration and irradn. with 14 MeV electrons under hyperbaric O (HPO) was measured. A std. dose of 80 mg I/kg injected into the tumor, followed by citrovorum rescue 24 h afterwards, produced a small but significant tumor response. There was no effect on the response of tumors of 1000 rad under HPO when I was given 7 days before irradn., but there was an increase in response, which was essentially additive, when the drug was given as a 24 h pretreatment. O concn. measurements showed no difference in rate or degree of oxygenation between pretreatment and control groups. A dose of 3000 rad under HPO was followed 7 days later by I administration, and gave an increased effect on the tumors which was more than additive. Early skin reactions were essentially the same for groups given combined treatment or irradn. only. Possible mechanisms involved, long term survival of the mice, and metastatic spread from the primary tumor are discussed.