PMID- 1922144
OWN - NLM
STAT- MEDLINE
DCOM- 19911031
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 253
IP  - 2
DP  - 1991 Oct
TI  - Inhibition of dinitropyrene mutagenicity in vitro and in vivo using Salmonella 
      typhimurium and the intrasanguinous host-mediated assay.
PG  - 181-91
AB  - Dinitropyrenes (DNP), present in polluted air, are potent direct-acting mutagens 
      in Salmonella typhimurium TA98. This mutagenicity is markedly reduced in the 
      presence of rat-liver S9 or microsomes. This has now been confirmed using mouse 
      hepatic fractions. Since most in vitro test systems do not adequately simulate 
      conditions encountered in the intact animal, we have investigated dinitropyrene 
      mutagenicity to Salmonella in the host-mediated assay. 1,8-Dinitropyrene 
      (1,8-DNP) given p.o. to BALB/c mice induced a weak mutagenic effect in S. 
      typhimurium TA98 recovered from the liver 1 h after i.v. administration (optimum 
      time). Over the entire dose range tested no toxicity to bacterial cells was 
      detected. Mutation induction in vivo was dose-related with maximum response at 1 
      mg DNP/kg body weight. This optimum dose, however, was non-mutagenic to strains 
      TA98/1,8-DNP6 (O-transacetylase-deficient) or TA98NR/1,8-DNP6 (nitroreductase- 
      and O-transacetylase-deficient). 1,3-Dinitropyrene and 1,6-dinitropyrene were 
      weakly mutagenic to TA98 at doses similar to 1,8-DNP. Studies with [14C]1,8-DNP 
      showed that 1 h after oral dosing (1 mg/kg), over 100 ng of 1,8-DNP equivalents 
      were present in the liver (= 0.73% dose). However, only about 5.5 ng were present 
      in the bacterial pellet, suggesting that hepatic components in vivo, as in vitro, 
      bind to DNP, thus interfering with its interaction with Salmonella.
FAU - Shah, A B
AU  - Shah AB
AD  - School of Biological Sciences, Portsmouth Polytechnic, Hants, Great Britain.
FAU - Rowland, I R
AU  - Rowland IR
FAU - Combes, R D
AU  - Combes RD
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Mutagens)
RN  - 0 (Pyrenes)
RN  - 51U7E9MW6I (1,8-dinitropyrene)
RN  - 66Q2ZUF83N (1,6-dinitropyrene)
RN  - D09D9L0924 (1,3-dinitropyrene)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Inactivation, Metabolic
MH  - Injections, Intravenous
MH  - Liver/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microsomes, Liver/metabolism
MH  - Mutagenicity Tests/*methods
MH  - *Mutagens
MH  - Pyrenes/administration & dosage/pharmacokinetics/*toxicity
MH  - Salmonella typhimurium/genetics
EDAT- 1991/10/01 00:00
MHDA- 1991/10/01 00:01
CRDT- 1991/10/01 00:00
PHST- 1991/10/01 00:00 [pubmed]
PHST- 1991/10/01 00:01 [medline]
PHST- 1991/10/01 00:00 [entrez]
AID - 0165-1161(91)90131-Q [pii]
AID - 10.1016/0165-1161(91)90131-q [doi]
PST - ppublish
SO  - Mutat Res. 1991 Oct;253(2):181-91. doi: 10.1016/0165-1161(91)90131-q.