PMID- 12438015
OWN - NLM
STAT- MEDLINE
DCOM- 20030117
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 521
IP  - 1-2
DP  - 2002 Nov 26
TI  - Effect of 10-aza-substitution on benzo[a]pyrene mutagenicity in vivo and in 
      vitro.
PG  - 187-200
AB  - Benzo[a]pyrene (BaP), an environmental carcinogen, shows genotoxicity after 
      metabolic transformation into the bay-region diol epoxide, BaP-7,8-diol 
      9,10-epoxide. 10-Azabenzo[a]pyrene (10-azaBaP), in which a ring nitrogen is 
      located in the bay-region, is also a carcinogen and shows mutagenicity in the 
      Ames test in the presence of the rat liver microsomal enzymes. In order to 
      evaluate the effect of aza-substitution on in vivo genotoxicity, BaP and 
      10-azaBaP were assayed for their in vivo mutagenicity using the lacZ-transgenic 
      mouse (MutaMouse). BaP was potently mutagenic in all of the organs examined 
      (liver, lung, kidney, spleen, forestomach, stomach, colon, and bone marrow), as 
      described in our previous report, whereas, 10-azaBaP was slightly mutagenic only 
      in the liver and colon. The in vitro mutagenicities of BaP and 10-azaBaP were 
      evaluated by the Ames test using liver homogenates prepared from several sources, 
      i.e. CYP1A-inducer-treated rats, CYP1A-inducer-treated and non-treated mice, and 
      humans. BaP showed greater mutagenicities than 10-azaBaP in the presence of a 
      liver homogenate prepared from CYP1A-inducer-treated rodents. However, 10-azaBaP 
      showed mutagenicities similar to or more potent than BaP in the presence of a 
      liver homogenate or S9 from non-treated mice and humans. These results indicate 
      that 10-aza-substitution markedly modifies the nature of mutagenicity of 
      benzo[a]pyrene in both in vivo and in vitro mutagenesis assays.
FAU - Yamada, Katsuya
AU  - Yamada K
AD  - Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University, 
      Tanabedori, Mizuho-ku, Nagoya 467-8603, Japan.
FAU - Suzuki, Takayoshi
AU  - Suzuki T
FAU - Kohara, Arihiro
AU  - Kohara A
FAU - Hayashi, Makoto
AU  - Hayashi M
FAU - Hakura, Atsushi
AU  - Hakura A
FAU - Mizutani, Takaharu
AU  - Mizutani T
FAU - Saeki, Ken-ichi
AU  - Saeki K
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Benzopyrenes)
RN  - 0 (Mutagens)
RN  - 189-92-4 (10-azabenzo(a)pyrene)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Benzo(a)pyrene/*chemistry/*toxicity
MH  - Benzopyrenes/chemistry/*toxicity
MH  - Cytochrome P-450 CYP1A1/drug effects/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Microsomes, Liver/drug effects/metabolism
MH  - Molecular Sequence Data
MH  - Mutagenicity Tests/methods
MH  - Mutagens/chemistry/*toxicity
MH  - Mutation
MH  - Salmonella typhimurium/drug effects/genetics
MH  - Structure-Activity Relationship
EDAT- 2002/11/20 04:00
MHDA- 2003/01/18 04:00
CRDT- 2002/11/20 04:00
PHST- 2002/11/20 04:00 [pubmed]
PHST- 2003/01/18 04:00 [medline]
PHST- 2002/11/20 04:00 [entrez]
AID - S1383571802002401 [pii]
AID - 10.1016/s1383-5718(02)00240-1 [doi]
PST - ppublish
SO  - Mutat Res. 2002 Nov 26;521(1-2):187-200. doi: 10.1016/s1383-5718(02)00240-1.