Development of test systems for the detection of compounds that prevent the genotoxic effects of heterocyclic aromatic amines: preliminary results with constituents of cruciferous vegetables and other dietary constituents.
Over the past decades, strong efforts have been made to identify dietary constituents that protect against the genotoxic effects of heterocyclic aromatic amines (HAAs). However, most of the methods that have been used, in particular in vitro assays that require the addition of exogenous enzyme homogenates, have only a limited predictive value because important protective mechanisms are not adequately represented and may give misleading results. Therefore, we attempted to develop improved test systems, namely assays, with human hepatoma cells and single-cell gel electrophoresis (SCGE) tests with rats. Genotoxicity tests with human derived Hep G2 cells reflect the genotoxic effects of HAAs better than other in vitro systems. They also enable the detection of protective effects since the human derived hepatoma cells possess phase I and phase II enzymes that are involved in the activation/ detoxification of the amines. The most appropriate endpoint for experiments with Hep G2 cells appears to be micronucleus induction, but protocols for other endpoints are available as well. The second promising model is the SCGE ("comet") assay with rats that was used successfully to measure protective effects of constituents of cruciferous vegetables against 2-amino-3-methylimidazo[4,5-flquinoline (IQ) in the liver and in the colon mucosa. The present study describes the experimental design of the new approaches, as well as results obtained with various dietary constituents.
Schwab
C
C
Institute for Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna.
Kassie
F
F
Qin
H M
HM
Sanyal
R
R
Uhl
I M
IM
Hietsch
G
G
Rabot
S
S
Darroudi
F
F
Knasmüller
S
S
D000818:Animals; D016587:Antimutagenic Agents / Q000145:classification / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D018890:Chemoprevention; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004032:Diet; D006571:Heterocyclic Compounds / Q000633:toxicity*; D006801:Humans; D010936:Plant Extracts / Q000145:classification / Q000494:pharmacology*; D051381:Rats; D014675:Vegetables / Q000737:chemistry*
D016587:Antimutagenic Agents; D006571:Heterocyclic Compounds; D010936:Plant Extracts