IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

Table 4 (contd)
Details of study Compound, route
and dose
Adduct formation in DNA of several organs of male Wistar rats given a
single dose of AAI and sacrificed 1 day and 1, 2, 4, 16 and 36 weeks later.
The nuclease P1 enhancement of the 32 P-postlabelling method was used to
analyse adducts in forestomach, glandular stomach, liver, lung and urinary
bladder. In the target organ (forestomach), dA-AAI and dG-AAI adducts
were removed rapidly within the first 2 weeks; thereafter, extensive
removal of the dG-AAI continued, whereas dA-AAI remained at constant
levels from 4 to 36 weeks.
Adduct formation in DNA of the forestomach of male BD-6 rats given
multiple doses of AA mixture. The nuclease P1 enhancement of the 32 Ppostlabelling
method was used to analyse adducts in forestomach. Chronic
diallyl sulfide co-administration decreased adduct levels in forestomach
DNA.
Adduct formation in DNA of the forestomach of male Sprague Dawley rats
given multiple doses of AAI or AAII or AA mixture. The AA mixture
consisted of 65% AAI and 34% AAII. The nuclease P1 enhancement of the
32 P-postlabelling method was used to analyse adducts in forestomach.
Adduct spots were identified by co-chromatography with in-vitro prepared
standard compounds. Adduct formation with AAI was more efficient than
with AAII.
Adduct formation in DNA of the kidney of male Wistar rats given a single
dose of AAI and sacrificed 1 day and 1, 2, 4, 16 and 36 weeks later. The
nuclease P1 enhancement of the 32 P-postlabelling method was used to
analyse adducts. The dA-AAI adduct showed lifelong persistence.
AAI, gavage,
5 mg/kg bw
AA mixture, gavage,
10 mg/kg bw twice a
week for 12 weeks
AAI or AAII or AA
mixture, gavage,
10 mg/kg bw twice
a week for 2 weeks
AAI, gavage,
5 mg/kg bw
DNA binding Reference
Initial level in forestomach:
dA-AAI: 30/10 8 nucleotides,
dG-AAI: 21/10 8 nucleotides
Level after 36 weeks in
forestomach: dA-AAI: 2/10 8
nucleotides, dG-AAI: 0.4/10 8
nucleotides
Total level in forestomach:
87/10 8 nucleotides
Total level in forestomach
(dA and dG adducts):
AAI: 62/10 7 nucleotides
AAII: 2.5/10 7 nucleotides
AA: 3.2/10 7 nucleotides
Initial level in kidney:
dA-AAI: 6.5/10 8 nucleotides,
dG-AAI: 3.8/10 8 nucleotides
Level after 36 weeks in
kidney: dA-AAI: 1.6/10 8
nucleotides, dG-AAI: 0.5/10 8
nucleotides
Fernando
et al. (1993)
Hadjiolov
et al. (1993)
Stiborová
et al. (1994)
Bieler et al.
(1997)
SOME TRADITIONAL HERBAL MEDICINES 101