Exceptional tumor-initiating activity of 4-fluorobenzo[j]-fluoranthene on mouse skin: comparison with benzo[j]-fluoranthene, 10-fluoro-benzo[j]fluoranthene, benzo[a]pyrene, dibenzo[a,l]pyrene and 7,12-dimethylbenz[a]anthracene.
Exceptional tumorigenic potency was observed with 4-fluorobenzo[j]fuoranthene (4-fluoroB[j]F) relative to benzo[j]fluoranthene (B[j]F) and 10-fluorobenzo[j]fluoranthene (10-fluoroB[j]F) in a mouse skin initiation promotion bioassay. Comparison of the tumorigenic response obtained at total initiating doses of 50, 100, and 1000 nmol firmly established the greater tumorigenic potency of 4-fluoroB[j]F. B[j]F produced a significant tumorigenic response only at total initiating doses of 100 and 1000 nmol per mouse. 10-FluoroB[j]F produced a significant tumorigenic response only at the highest initiating dose, 1000 nmol per mouse. In contrast, 4-fluoroB[j]F produced a significant tumorigenic response at all three doses. At a total initiating dose of 50 nmol, a 90% incidence of tumor-bearing mice with an average of 3.05 tumors per mouse was observed with 4-fluoroB[j]F. A second initiation promotion bioassay was performed to establish the tumorigenic potency of 4-fluoroB[j]F relative to benzo[a]-pyrene (B[a]P), 7,12-dimethylbenz[a]anthracene (DMBA), and dibenzo[a,l]pyrene (DB[a,l]P). 4-FluoroB[j]F did exhibit significant tumor-initiating activity at doses of 10 and 25 nmol per mouse, inducing a 45 and 60% incidence of tumor-bearing mice with an average of 0.75 and 1.65 tumors per mouse, respectively. While B[a]P was not tumorigenic at these doses, DMBA and DB[a,l]P exhibited significant tumorigenic activity at doses of 1, 4, 10, and 25 nmol per mouse. DB[a,l]P induced a 95% incidence of tumor-bearing mice with an average of 5.0 tumors per mouse at a total initiator dose of 1 nmol. DMBA at this dose produced an 85% incidence of tumor-bearing mice with an average of 1.30 tumors per mouse. The results of these initiation promotion bioassays clearly demonstrate that 4-fluoroB[j]F is significantly more active than B[j]F, 10-fluoroB[j]F and B[a]P and less active than either DMBA or DB[a,l]P as a tumor initiator on mouse skin.
LaVoie
E J
EJ
Rutgers University, College of Pharmacy, Piscataway, NJ 08855-0789.
He
Z M
ZM
Meegalla
R L
RL
Weyand
E H
EH
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001564:Benzo(a)pyrene; D005260:Female; D005449:Fluorenes / Q000138:chemical synthesis / Q000627:therapeutic use*; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced*
D005449:Fluorenes; C076937:4-fluorobenzo(j)fluoranthene; C076906:10-fluorobenzo(j)fluoranthene; C027704:benzo(j)fluoranthene; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene