The principal objective is to evaluate the hypothesis that azaserine is carcinogenic because it induces somatic mutation. Azaserine is known to be a bacterial mutagen which has major effects on pancreas growth and differentiation, including induction of acinar cell carcinoma, while the incidence of tumors in other tissues is lower or negligible. We propose to evaluate the degree and type of DNA alkylation caused by azaserine in vivo and in vitro in order to answer the following questions: (1) Does azaserine serve as an alkylating agent for DNA in mammalian cells? (2) Is there evidence of DNA repair in pancreas following azaserine treatment? (3) Does azaserine produce potentially mutagenic changes in the DNA of pancreas to a greater extent than in liver, kidney, and other tissues in animals which have been treated systemically with the agent? (4) Is azaserine directly active in inducing any such changes in DNA, or is a metabolite or degradation product such as diazoacetate involved in the induction of such changes? If azaserine proves not to be an alkylating agent for DNA, then we will emphasize study of DNA repair, and look for other potentially mutagenic structural changes in DNA -- approaching questions (3) and (4) in regard to any such change which might be detected. Studies of alkylation will be conducted utilizing radioactive azaserine. DNA from rat tissues (or in vitro incubations) will be isolated, hydrolyzed, and chromatographed to separate abnormal nucleosides. Any abnormal nucleosides will be characterized by mass and ultraviolet spectroscopy. If alkylation is detected we will compare the degree of DNA alkylation in pancreas with that in other tissues which seem less or un-affected by azaserine. If a metabolite of azaserine rather than azaserine itself seems to be the "active" form then the metabolism of azaserine in pancreas, liver and kidney will be compared. DNA repair will be assessed by measuring release of DNA-bound-C14 derived from C14-azaserine, repair replication studies and alkaline sucrose gradient centrifugation of pancreatic DNA.