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Concentration-dependent mutation by alkylating agents in human lymphoblasts and Salmonella typhimurium: N-methyl-N-nitrosourethane and. beta. -propiolactone

Journal Article · · J. Natl. Cancer Inst.; (United States)
OSTI ID:5338064
; ;
The toxic and mutagenic effects of the alkylating agents N-methyl-N-nitrosourethane (MNUT) and ..beta..-propioactone (BPL) were quantitatively measured in human lymphoblasts and Salmonella typhimurium. Forward mutation to 6-thioguanine resistance was measured in the human lymphoblasts, and forward mutation to 8-azaguanine resistance was measured in the bacterial cells after equigenerational (1.5 doubling times) exposures. In both systems, the induced mutant fraction rose linearly as a function of concentration for BPL and was biphasic for MNUT. The responses of the two assay systems to eight alkylating agents were compared. The exposure of the cells to each alkylating agent was calculated as exposure concentration multiplied by the time of exposure, and allowance was made for the decomposition of the alkylating agents during exposure (integral exposure). Human cells were 2.5 to 13 times more sensitive than was S. typhimurium to the alkylating agents methyl methanesulfonate, ethyl methanesulfonate, propyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, methylnitrosourea, and MNUT. S. typhimurium cells were three times more sensitive to butyl methanesulfonate and 25 times more sensitive to BPL than were human cells.
Research Organization:
Massachusetts Inst. of Tech., Cambridge
DOE Contract Number:
EE-77-S-02-4267
OSTI ID:
5338064
Journal Information:
J. Natl. Cancer Inst.; (United States), Journal Name: J. Natl. Cancer Inst.; (United States) Vol. 63:4; ISSN JNCIA
Country of Publication:
United States
Language:
English

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Related Subjects

560302 -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
560306* -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMAL CELLS
ANTIMITOTIC DRUGS
BACTERIA
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
COMPARATIVE EVALUATIONS
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
IN VITRO
LACTONES
LEUKOCYTES
LYMPHOCYTES
MATERIALS
MICROORGANISMS
MUTAGENESIS
MUTATION FREQUENCY
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
SALMONELLA
SALMONELLA TYPHIMURIUM
SOMATIC CELLS