Transformation-selective apoptotic program triggered by farnesyltransferase inhibitors requires Bin1.

Neoplastic transformation sensitizes many cells to apoptosis. This phenomenon may underlie the therapeutic benefit of many anticancer drugs, but its molecular basis is poorly understood. We have used a selective and potent farnesyltransferase inhibitor (FTI) to probe a mechanism of apoptosis that is peculiarly linked to neoplastic transformation.

Effect of isopropyl-beta-D-thiogalactopyranosid induction of the lac operon on the specificity of spontaneous and doxorubicin-induced mutations in Escherichia coli.

Previous studies of doxorubicin-induced mutations employing F' lacl/lacO as an endogenous gene target have focused on properties of large deletions with 3' endpoints residing in the lacO region of the target gene. This study considers the influence of Lac repressor binding on the distribution of these deletions. Results of the DNA sequence level analysis of spontaneous and doxorubicin-induced i-d and lacO mutations in Escherichia coli uvrB- are reported for mutants isolated under conditions where Lac repression is relieved by isopropyl-beta-D-thiogalactopyranosid (IPTG; an inducer that prevents repressor binding to lacO).

Correlation of doxorubicin footprints with deletion endpoints in lacO of E. coli.

This study explored the possibility that the sequence location of doxorubicin-induced deletion endpoints might relate to DNA structural alterations caused by doxorubicin binding to DNA. The 3'-OH endpoints of doxorubicin-induced deletions terminating in the 35-bp region of lacO appear to distribute differently from spontaneous deletion endpoints. Doxorubicin-induced deletions focus in the 26-bp palindrome which is separated by a 9-bp region with no reverse complementary, whereas spontaneous deletion 3'-OH endpoints are found distributed throughout the operator region.