Extension of understanding of mechanism whereby chemical changes particularly alkylations, inhibit DNA synthesis and replication, emphasizing experiments to disclose the effects on discontinuous aspects of DNA synthesis. This is to be correlated with the effects of HN2 on transcription, separated into effects on specific RNA processes such as pre-ribosomal RNA formation, the polyadenylation of heterogenous Hn RNA and the conversion to mRNA. Study of these effects in terms of mitochondrial-RNAs, including the components transcribed intramitochondrially and those shown to be derived from the nucleus. Comparison of these effects in HN2 sensitive and resistant tumors as well as with alkylating agents other than HN2. Study of structure-activity relations for Pt(II)-complexes and comparisons with HN2. Study of the effect of HN2 on the adenyl cyclase-cAMP system in relation to the effects of alkylation and the development of resistance.
NIH ExPorter
NIH ExPorter