PMID- 12167312 OWN - NLM STAT- MEDLINE DCOM- 20030304 LR - 20190922 IS - 1011-1344 (Print) IS - 1011-1344 (Linking) VI - 67 IP - 3 DP - 2002 Jul TI - Effect of dye aggregation on triarylmethane-mediated photoinduced damage of hexokinase and DNA. PG - 139-48 AB - The observation that enhanced mitochondrial membrane potential is a prevalent cancer cell phenotype has provided the conceptual basis for the development of mitochondrial targeting as a novel therapeutic strategy for both chemo- and photochemotherapy of neoplastic diseases. Cationic triarylmethane (TAM(+)) dyes represent a series of photosensitizers whose phototoxic effects develop at least in part at the mitochondrial level. In this report we describe how the molecular structure of four representative TAM(+) dyes (Crystal Violet, Ethyl Violet, Victoria blue R, and Victoria pure blue BO) affects their efficiency as mediators of the photoinduced inactivation of two model mitochondrial targets, hexokinase (HK) and DNA. Our results have indicated that TAM(+) dyes efficiently bind to HK and DNA in aqueous media both as dye monomers and aggregates, with the degree of aggregation increasing with increasing the lipophilic character of the photosensitizer. The efficiency with which HK and DNA are damaged upon 532 nm photolysis of biopolymer-TAM(+) complexes was found to decrease upon increasing the degree of dye aggregation over these macromolecular templates. Comparative experiments carried out both in water and in D(2)O, and in air-equilibrated and nitrogen-purged samples have also indicated that, at least when Crystal Violet is used as the photosensitizer, the mechanism of macromolecular damage does not require the involvement of molecular oxygen to operate. This finding makes Crystal Violet a potential candidate for use in photochemotherapy of hypoxic or poorly perfused tumor areas. FAU - Lewis, Lavinia M AU - Lewis LM AD - University of Wisconsin, School of Pharmacy, Madison 53705 2222, USA. FAU - Indig, Guilherme L AU - Indig GL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - J Photochem Photobiol B JT - Journal of photochemistry and photobiology. B, Biology JID - 8804966 RN - 0 (Coloring Agents) RN - 9007-49-2 (DNA) RN - EC 2.7.1.1 (Hexokinase) RN - OP0UW79H66 (Methane) SB - IM MH - Coloring Agents/*chemistry MH - DNA/*drug effects MH - *DNA Damage MH - Hexokinase/*drug effects MH - Methane/analogs & derivatives/*pharmacology EDAT- 2002/08/09 10:00 MHDA- 2003/03/05 04:00 CRDT- 2002/08/09 10:00 PHST- 2002/08/09 10:00 [pubmed] PHST- 2003/03/05 04:00 [medline] PHST- 2002/08/09 10:00 [entrez] AID - S1011134402003081 [pii] AID - 10.1016/s1011-1344(02)00308-1 [doi] PST - ppublish SO - J Photochem Photobiol B. 2002 Jul;67(3):139-48. doi: 10.1016/s1011-1344(02)00308-1.