title: Methotrexate: assessment of in vivo clastogenicity and carcinogenicity.
abstract: The genotoxic and oncogenic potentials of methotrexate were studied in Sprague-Dawley rats. The rats received 0.1, 0.2, or 0.4 mg/kg of methotrexate as dietary admixtures on a 5 days on, 9 days off, regimen for 23 months. In the females of the high-dose group, there was a significant increase in mortality starting at 18 months. Significant increases in the number of rats with focal pulmonary interstitial fibrosis were seen in both sexes at the high-dose level. At the mid- and high-dose levels of both sexes, there was a significantly increased number of rats with myeloid and erythroid bone marrow hypoplasia. There was no evidence of either early onset or increased incidence of any tumor type in the treatment groups. Therefore, it is concluded that methotrexate does not have oncogenic potential. Also, at terminal sacrifice, bone marrow cells were harvested from selected animals on the last day of the 5-day dosing cycle and cytogenetic evaluation was performed. No significant increase in chromosomal aberrations was seen in any dose group relative to the control group. This observation further substantiates the absence of oncogenic potential due to methotrexate in rats.
authors: Wilbur G. Malcom Toxicology Laboratories, American Cyanamid Co., Pearl River, New York 10965.
authors: C
authors: C
authors: Hall
authors: P
authors: P
authors: Tham
authors: M
authors: M
authors: Manandhar
authors: M
authors: M
authors: Cheng
authors: J F
authors: JF
authors: Noble
authors: M
authors: M
authors: Iatropoulos
mesh_terms: D000818:Animals; D002273:Carcinogens; D005260:Female; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
chemical_list: D002273:Carcinogens; D009153:Mutagens; D008727:Methotrexate