Loss of heterozygosity in (LewisxF344)F-1 rat urinary bladder tumors induced with N-butyl-N-(4-hydroxybutyl)nitrosamine followed by dimethylarsinic acid or sodium L-ascorbate
Tx. Chen et al., Loss of heterozygosity in (LewisxF344)F-1 rat urinary bladder tumors induced with N-butyl-N-(4-hydroxybutyl)nitrosamine followed by dimethylarsinic acid or sodium L-ascorbate, JPN J CANC, 90(8), 1999, pp. 818-823
Dimethylarsinic acid (DMA), a main metabolite of arsenicals which are carci
nogenic in man, exerts tumor-promoting activity on rat urinary bladder carc
inogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), Sodi
um L-ascorbate (Na-AsA) is also a strong tumor promoter in this animal mode
l. In this study, we used (LewisxF344)F-1 rats to compare molecular alterat
ions in urinary bladder tumors caused big BBN followed by DMA or Na-AsA, Ma
le, 6-week-old rats were given 0.05% BBN In their drinking water for 4 week
s, and then the rats in group 1 were maintained with no Further treatment f
or 40 weeks, The animals of groups 2 and 3 were administered 0.01% DMA in t
heir drinking water (group 2) or 5% Na-AsA in the powder diet (group 3) aft
er the BEN treatment. Group 4 rats were given 0.05% BBN continuously for 36
weeks, At weeks 12, 20, 36 and 44, subgroups of rats were killed. Histopat
hological examination revealed promoting activity for DMA and, to a greater
extent, Na-AsA on urinary bladder carcinogenesis. Loss of heterozygosity (
LOH), detected with the polymerase chain reaction using 36 microsatellite m
arkers, was found to be present in 2 of 9 (22%) urinary bladder tumors afte
r treatment with DMA and 3 of 22 (14%) induced by continuous administration
with BBN, No LOH was, however, detected in urinary bladder tumors after tr
eatment with Na-AsA, The results thus suggest that the mechanisms of action
of these two promoters, DMA and Na-AsA, may differ in rat urinary bladder
carcinogenesis.