discussion of preceding paper

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DISCUSSION OF PRECEDING PAPER Gerald Oster Mount Sinai School of Medicine City University of New York New York, New York 10029 Vinyl chloride binds to serum albumin. This is demonstrated by my finding that vinyl chloride displaces the fluorescent hydrophobe probe 1 -anilinonaph- thalene-8-sulfate (ANS) bound to serum albumin, and the system loses its fluorescence. Thus, serum albumin can transport vinyl chloride. Serum albumin is synthesized at specific regions of the liver, notably around the portal vein,' so vinyl chloride may be localized there. ANS interacts with the hydrophobic portion of cytochrome P-450 to give a shift to 385 nm.' This is the so-called Type I binding characteristic of some chlorinated hydrocarbons. These facts suggest that vinyl chloride may be metabolized, at least in its initial stages, via the cytochrome P-450 system in the endoplasmic reticulum of the liver cells. Free radical reactions are implicated in liver metabolism of carbon tetra- chloride as shown from the decolorization of the stable free radical, diphenyl- picrylhydrazyl (DPPH) by microsomes from the liver of a rat which had been fed carbon tetra~hloride.~ I have found that microsomes will initiate the polym- erization of a vinyl monomer, as shown by the production of turbidity in a 7 percent aqueous solution of acrylonitrile. The polymerization reaction, because it is a chain reaction, is a much more sensitive detector of free radicals than is DPPH and, furthermore, does not have the pitfalls of the DPPH test (namely decoloration by hydrogen donors). Vinyl chloride could polymerize in the lipid portions of liver cell organelles only if the monomer concentration is high. Other- wise, the monomer would undergo reactions such as dehalogenation and epoxide formation. Nowhere in this symposium is the possible hazard of the polymer, polyvinyl chloride, considered. During the polymerization of vinyl chloride the polymer precipitates and entrains monomer. In closed storage areas for polyvinyl chloride sheets one notices the characteristic odor of vinyl chloride showing that the monomer level in the room is high. Warming polyvinyl chloride pipe releases some entrained monomer. During the polymerization there is also entrapment of free radicals due to retardation of termination of the growing chain radicals. That polyvinyl dust encountered in the bagging process contains trapped free radicals is shown by its electron spin resonance signal. One wonders whether this dust is harmful. Cer- tainly workers in the polymerization plant are exposed not only to high levels of monomer but also to high concentrations of these free radical-laden dust particles. As regards the plastic processers, all polyvinyl chloride plastics give an electron spin resonance signal which is increased by heating the plastic or exposing it to ultraviolet light (notably sunlight). REFERENCES 1. HAMASHIMA, Y., HUNTER & A. H. COONS. 1964. J. Cell. Biol. 20: 271. 2. EALING, T. E. & R. P. DIAUGUSTINE. 1971. Biochem. J. 123: 539. 3. DI LUUO, N. R. & A. D. HARTMAN. 1969. Exp. Mol. Pathol. 11: 38. 149

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DISCUSSION OF PRECEDING PAPER

Gerald Oster

Mount Sinai School of Medicine City University of New York New York, New York 10029

Vinyl chloride binds to serum albumin. This is demonstrated by my finding that vinyl chloride displaces the fluorescent hydrophobe probe 1 -anilinonaph- thalene-8-sulfate (ANS) bound to serum albumin, and the system loses its fluorescence. Thus, serum albumin can transport vinyl chloride.

Serum albumin is synthesized at specific regions of the liver, notably around the portal vein,' so vinyl chloride may be localized there. ANS interacts with the hydrophobic portion of cytochrome P-450 to give a shift to 385 nm.' This is the so-called Type I binding characteristic of some chlorinated hydrocarbons. These facts suggest that vinyl chloride may be metabolized, at least in its initial stages, via the cytochrome P-450 system in the endoplasmic reticulum of the liver cells.

Free radical reactions are implicated in liver metabolism of carbon tetra- chloride as shown from the decolorization of the stable free radical, diphenyl- picrylhydrazyl (DPPH) by microsomes from the liver of a rat which had been fed carbon tetra~hloride.~ I have found that microsomes will initiate the polym- erization of a vinyl monomer, as shown by the production of turbidity in a 7 percent aqueous solution of acrylonitrile. The polymerization reaction, because it is a chain reaction, is a much more sensitive detector of free radicals than is DPPH and, furthermore, does not have the pitfalls of the DPPH test (namely decoloration by hydrogen donors). Vinyl chloride could polymerize in the lipid portions of liver cell organelles only if the monomer concentration is high. Other- wise, the monomer would undergo reactions such as dehalogenation and epoxide formation.

Nowhere in this symposium is the possible hazard of the polymer, polyvinyl chloride, considered. During the polymerization of vinyl chloride the polymer precipitates and entrains monomer. In closed storage areas for polyvinyl chloride sheets one notices the characteristic odor of vinyl chloride showing that the monomer level in the room is high. Warming polyvinyl chloride pipe releases some entrained monomer.

During the polymerization there is also entrapment of free radicals due to retardation of termination of the growing chain radicals. That polyvinyl dust encountered in the bagging process contains trapped free radicals is shown by its electron spin resonance signal. One wonders whether this dust is harmful. Cer- tainly workers in the polymerization plant are exposed not only to high levels of monomer but also to high concentrations of these free radical-laden dust particles. As regards the plastic processers, all polyvinyl chloride plastics give an electron spin resonance signal which is increased by heating the plastic or exposing it to ultraviolet light (notably sunlight).

REFERENCES 1. HAMASHIMA, Y. , HUNTER & A. H. COONS. 1964. J. Cell. Biol. 20: 271. 2. EALING, T. E. & R. P. DIAUGUSTINE. 1971. Biochem. J. 123: 539. 3. DI LUUO, N. R. & A. D. HARTMAN. 1969. Exp. Mol. Pathol. 11: 38.

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