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Hepatocarcinogenesis in the preweanling male B6C3F/sub 1/ mouse with alkenylbenzene derivatives: hepatic DNA adducts, structure-carcinogenicity relationships, and activating mutations in the C-HA-ras proto-oncogene

Thesis/Dissertation ·
OSTI ID:6583761
Hepatomas can be induced in preweanling male B6C3F/sub 1/ mice by a single carcinogen treatment. Several alkenylbenzene derivatives related to the naturally occurring hepatocarcinogens safrole and estragole have been examined in this sensitive system. New DNA adducts formed by reaction of 1'-acetoxy derivative of safrole and estragole at the C-8 and N-7 positions of guanine were characterized; they were also demonstrated in the hepatic DNA of 12-day-old B6C3F/sub 1/ mice treated with (/sup 3/H)-1'-hydroxysafrole (HOS). Likewise, adducts tentatively identified in earlier work as N/sup 2/-(safrol-1'-yl)- or N/sup 2/-(estragol-1'-yl)-deoxyguanosine were each characterized and resolved into a pair of diastereomers. Analogous N/sup 2/-adducts were characterized and shown to account for 85% of the hepatic DNA adducts formed by (/sup 3/H)-1'-hydroxy-2',3'-dehydroestragole (HOHDE). Induction of apurinic/apyrimidinic sites in supercoiled DNA differed 20-fold for 7 electrophilic alkenylbenzene derivatives. Although the mutagenic activities of these electrophiles in Salmonella typhimurium TA100 generally correlated well with B6C3F/sub 1/ hepatoma induction by the parent 1'- or 3'-hydroxy derivatives, the mutagenic and carcinogenic activities did not correlate with apurinic/apyrimidinic site induction.
Research Organization:
Wisconsin Univ., Madison (USA)
OSTI ID:
6583761
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMALS
AROMATICS
AZAARENES
BENZENE
BODY
CARCINOGENESIS
CHEMICAL COMPOSITION
DIGESTIVE SYSTEM
DISEASES
DNA ADDUCTS
GENES
GLANDS
GUANOSINE
HEPATOMAS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
LIVER
MAMMALS
MICE
MUTATIONS
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PURINES
RIBOSIDES
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
VERTEBRATES