Tumorigenicity in newborn mice of fjord region and other sterically hindered diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene), 4H-cyclopenta[def]chrysene and fluoranthene. 1995

S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
American Health Foundation, Valhalla, NY 10595, USA.

Diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[def,p]chrysene), 4H-cyclopenta[def]chrysene and fluoranthene were tested for tumorigenicity in newborn mice. The compounds tested were racemic trans-11,12-dihydroxy-anti-13,14-epoxy-11,12,13, 14-tetrahydrobenzo[g]-chrysene (BgCDE), trans-11, 12-dihydroxy-anti-13,14-epoxy-11,12,13,14-tetrahydrodibenzo [a,l]pyrene (DB[a,l]PDE), trans-1,2-dihydroxy-anti-3, 3a-epoxy,1,2,3,3a-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-1,3a-DE), trans-6,7-dihydroxy-anti-8,9-epoxy-10b,1, 2,3-tetrahydrofluoranthene (FDE). BgCDE and DB[a,l]PDE are fjord region diol epoxides and their tumorigenic activities were compared to those of trans-3,4-dihydroxy-anti-1, 2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPDE), a fjord region diol epoxide with known high tumorigenicity and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]-pyrene (BPDE), a highly tumorigenic bay region diol epoxide. The protocol called for testing of each compound at a total dose of 25 nmol per mouse, administered on days 1, 7 and 15 of life, with killing at age 35 weeks. BgCDE had similar activity as BcPDE for induction of lung tumors and was more active than BcPDE for induction of liver tumors in male mice. Both compounds were significantly more tumorigenic than BPDE. DB[a,l]PDE was highly toxic. All mice died within 1 week of the first dose. It was then tested in a second study using total doses of 5 and 1 nmol per mouse. Only the first dose of the intended 5 nmol total dose was given due to toxicity. The full course of doses with a total of 1 nmol per mouse was administered; DB[a,l]PDE induced a significant incidence and multiplicity of lung tumors and, in male mice, liver tumors at both doses. These results demonstrate that fjord diol epoxides are highly active tumorigens in newborn mice, with activity greater than that of the most active unsubstituted bay region diol epoxide, BPDE. C[def]C-1-3a-DE and C[def]-6-9-DE were compared to trans-1,2-dihydroxy-anti-3, 4-epoxy-1,2,3,4-tetrahydrochrysene (CDE), at a total dose of 500 nmol per mouse. FDE was also tested at this dose. The most active compound among the chrysene derivatives was C[def]C-1-3a-DE, followed by C[def]C-6-9-DE and CDE. C[def]C-1-3a-DE has a sterically constrained bay region, in which the benzylic carbon of the tri-substituted epoxide ring is part of a fused ring system. This feature is also present in FDE, which and considerable tumorigenic activity, greater than that of CDE in lung and greater than any of the chrysene derivatives in liver.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002911 Chrysenes 1,2-Benzphenanthrenes. POLYCYCLIC COMPOUNDS obtained from coal tar.
D005260 Female Females
D005449 Fluorenes A family of diphenylenemethane derivatives.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals

Related Publications

S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
September 1998, Carcinogenesis,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
September 2011, Chemical research in toxicology,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
January 1994, Chemical research in toxicology,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
March 1981, Cancer research,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
March 2017, Toxicology letters,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
July 1981, Cancer research,
S Amin, and D Desai, and W Dai, and R G Harvey, and S S Hecht
December 2011, Toxicology and applied pharmacology,
Copied contents to your clipboard!