Carcinogenesis In Female C57Bl/6J Mice
Chronically Exposed To Sodium Arsenate (AsV)
In Drinking Water For 2 Years
Author(s)
M. Krishnamohan, A. A. Seawright, M. R. Moore & J. C. Ng
Abstract
Arsenic is a ubiquitous element in the environment and has been classified as a
human carcinogen primarily based on epidemiological evidence. It has been
estimated there are over 100 million people globally being exposed to elevated
arsenic from both natural and anthropogenic sources. Surprisingly, positive
carcinogenicity animal studies were lacking until recent years. We aim to
validate inorganic arsenate carcinogenic effect in C57Bl/6J mice, and establish
the dose-response relationship using environmental concentrations of arsenic
similar to those found in typical endemic-areas. Mice were given 0, 100, 250 or
500 μg As/L in the form of sodium arsenate in drinking water ad libitum over 2
years. Tumours occurred after about 18 months of arsenic exposure otherwise
the animals appeared to be normal in their appearance and behaviour. Incidences
of all types of tumours and non-tumourous lesions in the treated groups were
higher than those observed in the control group. The induction of tumours was in
a dose-response manner for some tumour types. Enlargement of the mesenteric
lymph node due to hyperplasia or neoplasia of lymphoid elements was
commonly observed. Apart from abdominal cavity lymph nodes, tumours were
frequently observed in the liver, spleen and intestinal wall, and to a lesser extent
in the lung with various other tissues also occasionally affected. Of the
non-tumourous lesions, haemorrhagic ovarian cysts occurred more frequently in
the treated groups than in the control group. Our results suggest that the
C57Bl/6J mouse model can be a useful adjunct for further mechanistic studies of
arsenic carcinogenesis. This bioassay data may also be considered for the risk
evaluation of chronic exposure to inorganic arsenic.
Keywords
arsenic, arsenate, carcinogenesis, tumours, lymphoma, mice, drinking water, chronic exposure, risk assessment
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