Mutagenicity and tumorigenicity of dihydrodiols, diol epoxides, and other derivatives of benzo(f)quinoline and benzo(h)quinoline.
The mutagenic activities of benzo[f]quinoline, benzo[h]quinoline, and a number of their derivatives, including dihydrodiols, K-region oxides, diol epoxides, and tetrahydroepoxides, were assessed in strain TA 100 of Salmonella typhimurium. The dihydrodiol derivatives of benzo[f]quinoline and benzo[h]quinoline were also tested for tumorigenic activity in newborn mice. Benzo[f]quinoline was metabolically activated in the presence of rat liver S-9 preparation to products mutagenic to the bacterial system to a greater extent than was benzo[h]quinoline. However, trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline was less mutagenic compared to trans-7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline in the presence of rat liver homogenate. The data on the mutagenic activity of the dihydrodiol derivatives of benzoquinolines were consistent with the intrinsic mutagenicity of the corresponding epoxide derivatives, in that the bay-region diol epoxides and tetrahydroepoxide of benzo[h]quinoline exhibited considerably higher mutagenic activities compared to those of the corresponding derivatives of benzo[f]quinoline at equivalent doses. The K-region oxides of benzo[f]quinoline and benzo[h]quinoline were significantly less mutagenic than their corresponding bay-region diol epoxide and tetrahydroepoxide derivatives. The demonstration that benzo[f]quinoline is significantly more mutagenic than trans-7,8-dihydro-7,8-dihydroxybenzo[f]quinoline, a precursor to the weakly mutagenic bay-region diol epoxide, suggests that the bay-region diol epoxide formation is not the principal pathway for the metabolic activation of benzo[f]quinoline to a mutagen. On the other hand, the isomeric benzo[h]quinoline appears to exert its mutagenic effect via the formation of its bay-region diol epoxide. These results indicate that the position of a nitrogen heteroatom in phenanthrene (the analogous carbocyclic aromatic hydrocarbon) not only has a marked effect on the mutagenic activities of the diol epoxide derivatives, but also can alter the metabolic activation pathways of the parent hydrocarbon. Benzo[f]quinoline, benzo[h]quinoline, and their dihydrodiol derivatives were not tumorigenic in newborn mice.
Kumar
S
S
Great Lakes Laboratory, State University of New York College, Buffalo 14222.
Sikka
H C
HC
Dubey
S K
SK
Czech
A
A
Geddie
N
N
Wang
C X
CX
LaVoie
E J
EJ
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009153:Mutagens / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010616:Phenanthrenes / Q000378:metabolism / Q000633:toxicity; D011804:Quinolines / Q000378:metabolism / Q000633:toxicity*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D009153:Mutagens; D010616:Phenanthrenes; D011804:Quinolines; C031181:phenanthrene; C039108:benzo(f)quinoline