Summary: Cisplatin is a widely used chemotherapeutic agent. However, its clinical use is associated with induction of secondary tumors in patients. Oxaliplatin is less mutagenic than cisplatin in bacteria, but its mutagenicity in human cells has not been reported. Both cisplatin and oxaliplatin primarily form intrastrand crosslinks in DNA. One of the postulated mechanisms of mutagenesis is error-prone translesion synthesis. DNA polymerases beta and eta are capable of bypassing platinum-DNA adducts efficiently in vitro. We hypothesized that pol beta and pol eta are involved in translesion synthesis past cisplatin and oxaliplatin adducts in vivo. Our results indicated that pol eta is more efficient than pol beta in generating one-base frameshift errors during bypass of platinum-DNA adducts, and that both polymerases were able to generate 4--8 base deletions in the vicinity of the adducts. These results offer insights into the mechanisms of platinum-induced frameshift mutagenesis. Secondly, we report that the efficiency of error-free translesion synthesis by pol eta past platinum-GG adducts was very similar to that observed for this polymerase when the template contains thymine-thymine dimers. This finding suggests that pol eta could play a role in translesion synthesis past platinum-GG adducts in vivo. On the other hand, translesion synthesis past platinum-GG adducts by pol beta was much less efficient. Thirdly, we found that cisplatin-induced mutation frequencies in human fibroblasts lacking pol eta were higher than in those with either normal or high levels of expression of pol eta. These results suggest that pol eta is involved in error-free translesion synthesis past cisplatin adducts. We also found that at equitoxic doses cisplatin was less mutagenic than UVC. In contrast, oxaliplatin did not induce any mutations above background levels, suggesting that oxaliplatin is non-mutagenic in human fibroblasts. Lastly, we began developing a sensitive and specific method for detection of platinum adducts in vivo using mass spectrometry, and to date we have observed that this method is much more sensitive than atomic absorption. The experiments described in this dissertation were designed to identify and characterize several aspects of Pt-induced mutagenesis, which may ultimately lead to the development of highly effective, non-carcinogenic chemotherapeutic agents.