Four alkylating agents, β-propiolactone, 3-iodopropionic acid, 3-chloropropionic acid, and iodoacetic acid, were compared as initiators of mouse skin tumors, β-Propiolactone showed high activity; 3-iodopropionic acid had low activity; and 3-chloropropionic acid and iodoacetic acid showed no activity as initiators. In addition, the tritiated alkylating agents were tested for binding to skin DNA, RNA, and protein. The maximum binding of β-propiolactone to skin DNA in vivo was nearly 4 times higher than that of the weak initiator 3-iodopropionic acid, 10 times higher than that of the non-initiator 3-chloropropionic acid, and 20 times higher than that of the non-initiator iodoacetic acid. No such correlation with tumor initiating ability was found for binding to RNA or protein. These findings support the view that DNA is the significant cellular receptor of carcinogenic alkylating agents, in accordance with the somatic mutation theory of carcinogenesis.
This work was supported in part by grants from the American Cancer Society (E-6), the Alexander and Margaret Stewart Trust Fund, and the USPHS (CRTY-5002).