Teratogen metabolism: activation of thalidomide and thalidomide analogues to products that inhibit the attachment of cells to concanavalin A coated plastic surfaces. Revised version

Technical Report · Fri Jan 01 00:00:00 EST 1982

OSTI ID:5269153

Braun, A G; Weinreb, S L

Thalidomide metabolites inhibit the attachment of tumor cells to concanavalin A coated polyethylene surfaces. Thalidomide, itself, is non-inhibitory. Thalidomide activation to inhibitory products requires hepatic microsomes, an NADPH generating system and molecular oxygen. Production of inhibitory metabolites is unaffected by either epoxide hydrolase or TCPO, an inhibitor of epoxide hydrolase endogenous to hepatic S9 fraction. Therefore the attachment inhibitor is probably not an arene oxide. Inhibition is not accompanied by cytotoxicity as judged by trypan blue exclusion. Although uninduced hepatic microsomes from mice, rats and dogs have similar ability to activate thalidomide, microsomes from Aroclor 1254 induced rats are relatively inactive in the system. Inhibitory metabolites can be generated from the thalidomide analogues EM8, EM12, EM16, EM87, EM136, EM255, E350, phthalimide, phthalimido-phthalimide, indan, 1-indanone and 1,3-indandione. Glutarimide, glutamic acid and phthalic acid do not activate to inhibitory products.

• Research Organization: Harvard Medical School, Boston, MA (USA). Dept. of Radiation Therapy
• DOE Contract Number: AC02-82ER60070
• OSTI ID: 5269153
• Report Number(s): DOE/ER/60070-T1; ON: DE84006118
• Resource Relation: Other Information: Portions are illegible in microfiche products
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
MIXED-FUNCTION OXIDASES
METABOLIC ACTIVATION
TERATOGENS
METABOLISM
ASCITES
CELL CULTURES
CONCANAVALIN
EXPERIMENTAL DATA
IMIDES
INDAN
PHTHALIC ACID
AGGLUTININS
ANTIBODIES
AROMATICS
CARBOXYLIC ACIDS
DATA
DICARBOXYLIC ACIDS
ENZYMES
HEMAGGLUTININS
HYDROCARBONS
INFORMATION
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PATHOLOGICAL CHANGES
SYMPTOMS
550800* - Morphology
550500 - Metabolism