The goal of these experiments in female Hsd:(ICR)Br mice was to determine whether the direct-acting SN1 alkylating
carcinogen isopropyl methanesulfonate (IMS) is carcinogenic and to compare its effects with those of the direct-acting SN2 methyl homologue,
methyl methanesulfonate (MMS). The compounds were administered by topical application and s.c. injection. Analysis at the 288th day of mice receiving s.c.
injections of IMS and MMS was the subject of a previous report (A. Segal et al., Proc. Soc. Exp. Biol. Med., 183: 132-135, 1986). The s.c. and topical application experiments were terminated at the 450th day and the final results are reported in this paper. In mice treated by s.c. injection with IMS, thymic
lymphomas were observed in at least 20 of 32 mice, the first at the 40th day, and
neoplasms were not observed at the injection site. Of the 30 MMS-treated mice, 11 developed
sarcomas at the injection site and one thymic
lymphoma was observed. In mice treated topically with IMS, thymic
lymphomas were observed in 20 of 30 treated mice, the first at the 102nd day, and
squamous cell carcinomas at the injection site were observed in 9 mice. Neither
squamous cell carcinomas nor thymic
lymphomas were observed in 30 mice following topical application of MMS. The direct-acting SN2 aklylating
carcinogen beta-propiolactone was also administered by topical application. At the 450th day, at the same dose used for MMS (40 mumol/application),
papillomas of the skin were observed in 25 of 30 treated mice,
squamous cell carcinomas of the skin were seen in 17 mice, and one thymic
lymphoma was observed. The results suggest that the rapid induction of
thymomas by IMS may be related to its ability to alkylate exocyclic
oxygen atoms in
DNA of hemopoietic cells and also to a sensitivity of these cells to such lesions.