<i>Response</i>
            : Hydralazine Reactions

Dubroff, Lewis M.; Reid, Robert J.; Papalian, Michael M.; Alexander, Scott W.

doi:10.1126/science.214.4516.95

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…Such a reaction also proceeds with hydralazine. We have shown that a large percentage of thymine bases in DNA were modified and excised by hydralazine (16). The extent of the modification and excision was dependent on the concentration and time of exposure to drug.…”

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 98%

“…We have shown that hydralazine alters the pyrimidine bases of DNA (11,16). Modified DNA can be highly immunogenic (17).…”

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 98%

“…At higher concentrations hydralazine reacts with labeled deoxycytidine to form at least 3 products. Metabolites of hydralazine showed no significant reactivity with pyrimidine nucleosides (12). These metabolites include 3-methyl-s-triazolo [3,4-a] phthalazine (MTP), phthalazinone (PZ), pyruvic acid hydrazone (PYR), and glycolic acid conjugate of 3-hydroxymethyl-s-triazolo [3,4-a] phthalazine (HTP Gluc) (13).…”

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 99%

“…The reaction of DNA with hydralazine was analyzed by separation by thin layer chromatography and high performance liquid chromatography (16). Reaction products from thymidine labeled DNA incubated with hydrazine revealed at least 3 labeled products with chromatographic characteristics similar to the products obtained by the reaction of hydralazine with thymidine.…”

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 99%

See 3 more Smart Citations

Molecular models for hydralazine‐related systemic lupus erythematosus

Dubroff

Reid

Papalian

1981

Arthritis & Rheumatism

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Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 98%

“…We have shown that hydralazine alters the pyrimidine bases of DNA (11,16). Modified DNA can be highly immunogenic (17).…”

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 98%

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 99%

Section: Molecular Models For Hydralazine-related Systemic Lupus Erytmentioning

confidence: 99%

See 2 more Smart Citations

Molecular models for hydralazine‐related systemic lupus erythematosus

Dubroff

Reid

Papalian

1981

Arthritis & Rheumatism

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In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine)

Flora¹,

Zanacchi²,

Bennicelli³

et al. 1982

Environ. mutagen

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Three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine) were found to be genotoxic in four in vivo or in vitro short-term test systems. a) In mice, a single ip administration of the LD50 of the three drugs caused a small but statistically significant increase over controls in DNA elution rate, ie, a modest amount of DNA fragmentation, in three of the four organs (liver, lung, kidney, and spleen) tested, DNA damage being absent in lung for hydralazine and endralazine and in liver for dihydralazine. Only for hydralazine DNA lesions were always repaired within 12 hr, in agreement with the constant lack of cumulative effects in mice given five successive daily doses. The rank of potencies was hydralazine greater than dihydralazine greater than endralazine. b) In mice bone marrow cells, all three hydrazine derivatives induced a modest but statistically significant increase over controls in the frequency of sister chromatid exchanges, the rank of potencies being in this case dihydralazine greater than endralazine greater than hydralazine. c) In the Ames reversion test all three drugs behaved as direct-acting mutagens of low potency, whose activity was not influenced by rat liver nor by mouse liver or lung S-9 fractions. Hydralazine and dihydralazine elicited mixed genetic mechanisms of mutations, while endralazine exclusively induced frameshift errors in Salmonella DNA. The recently developed strain TA97 was the most efficient in revealing frameshift errors with all three drugs. d) The selective lethality assays in a battery of two S typhimurium and five E coli strains confirmed the direct genotoxicity of hydralazine, dihydralazine, and endralazine, in order of potency. Potency was evaluated by means of a sensitive and reliable micromethod procedure. Among those investigated, the recA recombination repair and the lexA post-replication repair ("SOS functions") and, to a lesser extent, also the polymerase I mechanism, appeared to contribute to the specific DNA repair with all three drugs, while excision repair systems (uvrA and uvrB) did not appear to be involved.

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S

Elks¹,

Ganellin²

1990

Dictionary of Drugs

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Response : Hydralazine Reactions

Cited by 4 publications

References 5 publications

Molecular models for hydralazine‐related systemic lupus erythematosus

Molecular models for hydralazine‐related systemic lupus erythematosus

In vivo and in vitro genotoxicity of three antihypertensive hydrazine derivatives (hydralazine, dihydralazine, and endralazine)

S

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