Procainamide-induced lupus erythematosus

Blomgren, Stephen E.; Condemi, John J.; Vaughan, John H.

doi:10.1016/0002-9343(72)90021-6

Cited by 198 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Individuals that develop this reaction have antinuclear antibodies as well as antibodies to DNA and nucleoproteins (6)(7)(8)(9)(10)(11)(12)(13). In vitro studies have also demonstrated interaction of systemic lupus erythematosus-inducing drugs with DNA (11,14,15).…”

mentioning

confidence: 99%

Relationship between the genetically determined acetylator phenotype and DNA damage induced by hydralazine and 2-aminofluorene in cultured rabbit hepatocytes.

McQueen

Maslansky

Glowinski

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The relationship between acetylation rates of rabbit hepatocytes and their susceptibility to genotoxicity by DNAdamaging chemicals that undergo N-acetylation was studied in primary cultures of hepatocytes from New Zealand White rabbits that have a genetically determined difference in acetylation rates. Hepatocytes from rapid and slow acetylator rabbits maintained in culture the difference in acetylation rates that existed in viva DNA repair, an index of DNA damage, was produced by hydralazine in hepatocytes from slow acetylator rabbits but not in those from rapid acetylators. In contrast to these results, hepatocytes from rapid acetylators were more sensitive than those from slow acetylators to toxicity from the carcinogen 2-aminofluorene and displayed greater amounts of DNA repair. The amount of DNA repair measured with either chemical was dose dependent. These phenotype-dependent differences in the genotoxicity of two DNAdamaging chemicals provide evidence for the role of the acetylation polymorphism as a factor in determining susceptibility to toxicity, and perhaps carcinogenicity, of these chemicals. N-Acetylation rates of xenobiotics are under polymorphic genetic control in both humans and rabbits, resulting in individuals being either rapid or slow acetylators (1-5). This trait has been linked to toxicity and damage to DNA by chemicals of the aromatic amine or hydrazine type (6). For example, slow acetylator individuals are more likely than rapid acetylators to develop drug-related systemic lupus erythematosus (6-8). Individuals that develop this reaction have antinuclear antibodies as well as antibodies to DNA and nucleoproteins (6)(7)(8)(9)(10)(11)(12)(13). In vitro studies have also demonstrated interaction of systemic lupus erythematosus-inducing drugs with DNA (11,14,15).In the metabolism ofxenobiotics, N-acetylation is a step that can be followed by reactions such as N-hydroxylation and esterification, resulting in the generation of reactive metabolites that undergo covalent binding with cellular macromolecules, including DNA (16,17). Chemicals that can be acetylated and that also form covalent adducts with DNA include procainamide (18,19), isoniazid (20), and hydralazine (15), as well as the aromatic amine carcinogens, benzidine (21, 22), 2-aminofluorene, and 4-aminobiphenyl (23). Adduct formation by chemicals can be mediated by the enzymatic removal of the N-acetyl moiety (24,25), and evidence in the rabbit suggests that this reaction and the initial acetylation step are properties of the same enzyme (26).Because a difference in the acetylation rate can alter the proportion ofspecific metabolites that are formed (27), it is possible that genotoxicity-i. e., damage to DNA (28)-by substrates of N-acetyltransferase could be affected by the amount of acetylation. In order to investigate this possibility, we developed a model system that permitted measurement of both N-acetyltransferase activity and DNA damage in the same cells, using hepatocytes, which represent a major tissue of acetylation (...

show abstract

mentioning

confidence: 99%

Relationship between the genetically determined acetylator phenotype and DNA damage induced by hydralazine and 2-aminofluorene in cultured rabbit hepatocytes.

McQueen

Maslansky

Glowinski

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Recent etiologic hypotheses for SLE suggest that, given a predisposition, an environmental factor, such as a drug or a viral infection, may elicit manifest disease (20,21). T h e study of monozygotic twins discordant for SLE thus provides a unique opportunity to study environmental influences that might explain the development of disease in only one of two individuals of identical genotype.…”

Section: Discussionmentioning

confidence: 99%

Monozygotic twins discordant for systemic lupus erythematosus

Yocum

Grossman

Waterhouse

et al. 1975

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

A pair of monozygotic twins discordant for systemic lupus erythematosus (SLE) were studied and no differences noted in their immune response to tetanus toxoid, keyhole lympet hemocyanin, DNCB, delayed sensitivity, or antibody titers to viruses. Both were noted to have biologically false positive serology at an early age, but only one twin developed SLE. The clinically unaffected twin underwent castration at an early age, suggesting that ovarian hormones may play an important role in the development of SLE.The various proposed etiologies of systemic lupus erythematosus (SLE) include viral infection (1). endocrine abnormality (2), genetic predisposition (3), and hypersensitivity to self with loss of immunologic

show abstract

“…One of the well-documented hazards of procainamide therapy is the development of systemic lupus erythematosis (Ladd, 1962;Blomgren, Condemi & Vaughan, 1972;Kosowsky, Taylor, Lown & Ritchie, 1973). This may present with polyarthralgia, myalgia, pleurisy or fever.…”

Section: Methodsmentioning

confidence: 99%

Adverse Reactions to Procainamide

1977

Inpharma

View full text Add to dashboard Cite

Procainamide-induced lupus erythematosus

Cited by 198 publications

References 29 publications

Relationship between the genetically determined acetylator phenotype and DNA damage induced by hydralazine and 2-aminofluorene in cultured rabbit hepatocytes.

Relationship between the genetically determined acetylator phenotype and DNA damage induced by hydralazine and 2-aminofluorene in cultured rabbit hepatocytes.

Monozygotic twins discordant for systemic lupus erythematosus

Adverse Reactions to Procainamide

Contact Info

Product

Resources

About