Our Science – Riesz Website

Peter Riesz, Ph.D.

Radiation Biology Branch Senior Investigator Building 10, Room B1B50 NCI-Radiation Biology Branch 9000 Rockville Pike Bethesda, MD 20892-1002 Phone:   301-496-4036 Fax:   301-480-2238 E-Mail:   sono@helix.nih.gov

Biography

Before joining the National Cancer Institute as a research chemist in 1958, Dr. Riesz was a research associate in the chemistry departments at the Argonne National Laboratory, Brookhaven National Laboratory, and Pennsylvania State University. He obtained his Ph.D. in physical chemistry at Columbia University in New York in 1953 and his B.A. and B.Sc. degrees at Oxford University in England in 1947.

Research

Electron Paramagnetic Resonance (EPR) Studies of Chemical and Biological Effects of Ultrasound, Light, and Ionizing Radiation

Recently it has been shown that the combination of ultrasound and certain drugs (sonosensitizers) is a promising modality for cancer treatment. The effectiveness of sonodynamic therapy has been demonstrated in cell studies and in tumor-bearing animals. Our studies indicate that the mechanism of this drug-dependent sonosensitization involves the formation of free radicals from the sonosensitizer that react with oxygen to form peroxyl and alkoxyl radicals that have a higher probability of reaching critical cellular sites than hydroxyl radicals and hydrogen atoms, which are initially formed by ultrasound in the cavitation bubbles. Our laboratory is focused on the detection and identification of free radical intermediates in sonochemistry (related to sonodynamic therapy) and radiation chemistry (related to radiation therapy). Some recent results and ongoing projects are summarized below:

- n-Alkyl glucopyranosides with hexyl-(5mM), heptyl-(3mM), or octyl-(2mM) n-alkylchains protected 100% of HL-60 cells from 1.057 MHz ultrasound under a range of conditions that resulted in 35 to 100% cytolysis in the absence of glucopyranosides.

- Using the temperature dependence of the kinetic deuterium isotope effect, we have estimated that the effective temperatures in collapsing cavitation bubbles in aqueous solutions are in the region of 2,000-4,000K.

- An EPR spin trapping investigation of the sonochemistry of neutral aqueous solutions has shown that hydrated electrons are not a significant intermediate. This is in agreement with the hot spot theory of sonochemistry and provides evidence against the electrical discharge theories.

- Low concentrations of gallium porphyrin ATX-70 significantly enhanced cellular toxicity in human leukemia HL-525 cells exposed to 50 kHz ultrasound. Extracellular localization of ATX-70 molecules was found to be effective for sonosensitization.

- Combination of focused ultrasound, which can penetrate deeply into tissue with sonodynamic sensitizers, may prove to be a useful approach for locally intensive chemotherapy.

- The effect of gas-containing microspheres and echo-contrast agents on free radical formation by ultrasound was studied. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the contrast agents lower the cavitation threshold of diagnostic ultrasound.

- The free radical intermediates formed during the ultrasound exposure of cell culture media were identified by EPR spin trapping. The dominant free radicals were derived from the hydrophobic amino acids Trp, Phe, Tyr, Leu, Val, and Met consistent with the accumulation of hydrophobic solutes at the liquid-gas interface of collapsing cavitation bubbles.

- The effects of cysteamine and cystamine on the sonochemical accumulation of hydrogen peroxide has been investigated. The protective effect of cysteamine and the lack of protection of cystamine on mammalian cells exposed to ultrasound is due to their differential abilities to lower hydrogen peroxide yields without the necessity of invoking intracellular cavitation.

This page was last updated on 6/12/2008.