Abstract
Paraquat and nitrofurantoin can accept single electrons and, under appropriate conditions in tissues and cells, can pass these electrons to oxygen, thus participating in redox cycling. Similarities in the response of the target organ (the lung) and in subsequent pathology have also been observed among animals poisoned by oxygen and by these chemicals. We report evidence primarily obtained from Escherichia coli for common biochemical sites of toxicity for these agents. Common sites for oxygen and paraquat involve biosynthesis of specific amino acids, induction of genetic stringency via unloaded tRNAs resulting from amino acid deficiencies, decreased thiamin content, and impaired biosynthesis of pyridine nucleotide coenzyme biosynthesis for paraquat and oxygen. Inhibition of specific amino acid biosynthesis and induction of stringency also have been observed for nitrofurantoin. RNA and DNA biosynthesis are also impaired by oxygen; this has not been examined for paraquat or nitrofurantoin. There is a biochemical basis and preliminary data to support inhibition of NAD biosynthesis as a component of mammalian toxicity for these agents. Niacin may act to circumvent the consequences of the biochemical lesion at quinolinate phosphoribosyl transferase in NAD biosynthesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 209-214 |
| Number of pages | 6 |
| Journal | Fundamental and Applied Toxicology |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1983 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Toxicology
Cite this
Oxygen and redox-active drugs : Shared toxicity sites. / Brown, Olen R.; Seither, Richard.
In: Fundamental and Applied Toxicology, Vol. 3, No. 4, 1983, p. 209-214.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oxygen and redox-active drugs
T2 - Shared toxicity sites
AU - Brown, Olen R.
AU - Seither, Richard
PY - 1983
Y1 - 1983
N2 - Paraquat and nitrofurantoin can accept single electrons and, under appropriate conditions in tissues and cells, can pass these electrons to oxygen, thus participating in redox cycling. Similarities in the response of the target organ (the lung) and in subsequent pathology have also been observed among animals poisoned by oxygen and by these chemicals. We report evidence primarily obtained from Escherichia coli for common biochemical sites of toxicity for these agents. Common sites for oxygen and paraquat involve biosynthesis of specific amino acids, induction of genetic stringency via unloaded tRNAs resulting from amino acid deficiencies, decreased thiamin content, and impaired biosynthesis of pyridine nucleotide coenzyme biosynthesis for paraquat and oxygen. Inhibition of specific amino acid biosynthesis and induction of stringency also have been observed for nitrofurantoin. RNA and DNA biosynthesis are also impaired by oxygen; this has not been examined for paraquat or nitrofurantoin. There is a biochemical basis and preliminary data to support inhibition of NAD biosynthesis as a component of mammalian toxicity for these agents. Niacin may act to circumvent the consequences of the biochemical lesion at quinolinate phosphoribosyl transferase in NAD biosynthesis.
AB - Paraquat and nitrofurantoin can accept single electrons and, under appropriate conditions in tissues and cells, can pass these electrons to oxygen, thus participating in redox cycling. Similarities in the response of the target organ (the lung) and in subsequent pathology have also been observed among animals poisoned by oxygen and by these chemicals. We report evidence primarily obtained from Escherichia coli for common biochemical sites of toxicity for these agents. Common sites for oxygen and paraquat involve biosynthesis of specific amino acids, induction of genetic stringency via unloaded tRNAs resulting from amino acid deficiencies, decreased thiamin content, and impaired biosynthesis of pyridine nucleotide coenzyme biosynthesis for paraquat and oxygen. Inhibition of specific amino acid biosynthesis and induction of stringency also have been observed for nitrofurantoin. RNA and DNA biosynthesis are also impaired by oxygen; this has not been examined for paraquat or nitrofurantoin. There is a biochemical basis and preliminary data to support inhibition of NAD biosynthesis as a component of mammalian toxicity for these agents. Niacin may act to circumvent the consequences of the biochemical lesion at quinolinate phosphoribosyl transferase in NAD biosynthesis.
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U2 - 10.1016/S0272-0590(83)80127-4
DO - 10.1016/S0272-0590(83)80127-4
M3 - Article
C2 - 6195038
VL - 3
SP - 209
EP - 214
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 4
ER -