Rapid induction of thymic lymphomas by isopropyl methanesulfonate: a preliminary report.
The direct-acting SN1 alkylating agent isopropyl methanesulfonate (IMS) was carcinogenic by subcutaneous injection in female Hsd:(ICR)BR mice, causing thymic lymphoid neoplasms within 7 months in at least 20 of 32 treated mice. No such neoplasms were observed in mice treated with the direct-acting SN2 methyl homolog, methyl methanesulfonate (MMS). Both the IMS-treated mice and the MMS-treated mice initially received 20 mumole of the respective compounds by sc injection once weekly; however, because of toxic effects the dose of IMS was reduced to 10 mumole per injection on the 63rd day and further reduced to 5 mumole per injection on the 120th day, after which this dose was maintained until the 202nd day when the last surviving IMS-treated mouse became moribund and was sacrificed. In 2 of the MMS-treated mice, 93% of which were alive at 288 days, tumors were observed at the site of injection, one being a papilloma and the other a subcutaneous sarcoma. IMS has not previously been implicated as a carcinogen, to our knowledge. Its induction of thymic lymphomas may conceivably be related to its ability to alkylate exocyclic oxygen atoms in the DNA of hemopoietic cells.
D000818:Animals; D005260:Female; D008206:Lymphatic Diseases / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced* / Q000473:pathology; D008698:Mesylates / Q000633:toxicity*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D013950:Thymus Gland / Q000473:pathology
D008698:Mesylates; D008741:Methyl Methanesulfonate; C002531:isopropylmethanesulfonate