Cytokinetic studies reveal etiology of cytogenetic genotoxicity produced by a series of angiotensin II (AII) receptor antagonists may be perturbed DNA synthesis

Conference · Fri Jan 01 00:00:00 EST 1993 · Cytometry (Baltimore); (United States)

OSTI ID:6831615

Selden, J R; Miller, J E; Dolbeare, F; Galloway, S M; Nichols, W W ^[1]

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1. Merck Research Laboratories, West Point, PA (United States) Lawrence Livermore National Lab., CA (United States)

Six of 13 AII receptor antagonists produced chromosomal aberrations in CHO cells. In addition, these six compounds perturbed cellular kinetics (i.e., reduced mitotic indices and cell yields). It was hypothesized that the mechanism of clastogenesis was not due to a direct genotoxic effect, but may result from disruption of DNA replication. Flow cytokinetic studies, using the BrdUrd-FITC/propidium iodide technique, were performed on all six clastogenic compounds, and a seventh candidate from this group. All seven altered CHO cell kinetics as follows: (1) The amount of BrdUrd per S phase cell was reduced; (2) Cell movement within S phase was inhibited; and (3) Lowest doses perturbing CHO cell kinetics were below minimum concentrations producing aberrations. These data provide evidence that this cytogenetic damage is mediated by a mechanism which disrupts cellular DNA synthesis.

• OSTI ID: 6831615
• Report Number(s): CONF-9303114-; CODEN: CYTODQ
• Journal Information: Cytometry (Baltimore); (United States), Vol. 6; Conference: 16. congress of the International Society for Analytical Cytology, Colorado Springs, CO (United States), 21-26 Mar 1993; ISSN 0196-4763
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANGIOTENSIN
INHIBITION
DNA
BIOSYNTHESIS
RECEPTORS
CELL CYCLE
CELL DIVISION
CHROMOSOMAL ABERRATIONS
CYTOLOGICAL TECHNIQUES
DNA REPLICATION
CARDIOVASCULAR AGENTS
DRUGS
GLOBULINS
MEMBRANE PROTEINS
MUTATIONS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
SYNTHESIS
VASOCONSTRICTORS
550300* - Cytology
550200 - Biochemistry