Detoxification of nitrosamides and nitrosocarbamates in blood plasma and tissue homogenates

Journal Article · Sun Jan 01 00:00:00 EST 1984 · Environ. Manage.; (United States)

DOI:https://doi.org/10.1002/em.2860060610· OSTI ID:5762192

Aukerman, S L; Brundrett, R B; Hartman, P E

Nitrosamides and nitrosocarbamates exhibit relatively high mutagenic activity in Salmonella when compared with nitrosoureas. In striking contrast to the in vitro mutagenicity tests, a number of studies have indicated that nitrosamides and nitrosocarbamates are less potent than nitrosoureas when tested in vivo in model systems such as the mouse. The authors extend here previous studies that demonstrate striking chemical decomposition and inactivation of mutagenic activity of nitrosamides and nitrosocarbamates during exposure to murine blood plasma. Plasma glutathione concentrations are inadequate to account for the rapid inactivations noted. Furthermore, the predominant inactivating species is heat-sensitive, nondialyzable, and is greater than 25,000 daltons in size as judged by ultrafiltration experiments. Mouse liver, large intestine, kidney, and stomach have more activity per milligram protein under the assay conditions used than plasma itself. Rat liver S9 is also active at enhancing the decomposition of nitrosamides and nitrosocarbamates; most of this inactivating capacity resides in the microsomal fraction. The relatively rapid detoxification of these N-nitroso compounds by plasma and other tissues of rodents has important implications regarding the utility of rodents in assessment of tumorigenicity and/or antitumor activity of these classes of drugs in other animal species.

• Research Organization: Johns Hopkins Univ., Baltimore, MD
• OSTI ID: 5762192
• Journal Information: Environ. Manage.; (United States), Vol. 6:6
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BLOOD PLASMA
DETOXIFICATION
NITROSO COMPOUNDS
CATABOLISM
MUTAGEN SCREENING
AMIDES
CARBAMATES
DECOMPOSITION
HOMOGENATES
MICE
SALMONELLA TYPHIMURIUM
ANIMALS
BACTERIA
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CHEMICAL REACTIONS
MAMMALS
MATERIALS
METABOLISM
MICROORGANISMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RODENTS
SALMONELLA
SCREENING
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)