Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium
Figure 10
Proposed mechanism of SIN-1 cytotoxicity. (a) Mechanism of the dependence of SIN-1 cytotoxicity on the total number of initial SIN-1 molecules per cell. SIN-1 decomposition yields a stable cytotoxic entity, which enters the cells and is promptly metabolized, resulting in cytotoxicity. Because of the rapid metabolism, cellular incorporation of the cytotoxic entity of SIN-1 is one directional, and therefore the cytotoxic effect is augmented when the volume of SIN-1-containing medium is increased with respect to the number of cells. (b) Potential cytotoxic entity of SIN-1. SIN-1-derived reacts with CO2 in the culture medium, resulting in the formation of . A small portion of the thus generated, or its derivatives, may be stabilized by forming a complex with SIN-1C or other SIN-1-derived breakdown products, which renders the complex chemically inert. However, interaction with cells converts it to cytotoxic substances.
