Carcinogenesis, Vol 18, 185-192, Copyright © 1997 by Oxford University Press
T Ichinose, Y Yajima, M Nagashima, S Takenoshita, Y Nagamachi and M Sagai
In order to clarify the involvement of oxygen radicals in lung
carcinogenesis induced by diesel exhaust particles (DEP), the relationship
between lung tumour response and formation of 8- hydroxydeoxyguanosine
(8-OHdG) in lung DNA was examined. The role of high dietary fat and
beta-carotene on these responses was also studied. Mice were
intratracheally injected with 0.05, 0.1 and 0.2 mg of DEP per animal once
weekly for 10 weeks. After 12 months, the lung tumour incidence in mice
treated with 0.05 mg and 0.1 mg showed similar increases (30% and 31%), but
was decreased to 24% at 0.2 mg. High dietary fat enhanced the incidence of
both benign and malignant tumours. beta-carotene partially prevented the
tumour development. After the 10 weekly treatments of DEP, inflammatory
reaction was observed in the respiratory tract and alveoli. The formation
of 8-OHdG in lung DNA from mice treated with DEP showed a dose dependent
increase. 8-OHdG formation was enhanced by high dietary fat and partially
reduced by beta-carotene. Formation of 8-OHdG was significantly correlated
with the lung tumour incidence except at 0.2 mg. These results suggest that
the induction of oxidative DNA damage may be an important factor in the
initiation of DEP-induced lung carcinogenesis, and that beta-carotene and
high dietary fat may play a role in the regulation of tumour development
via modulation of the formation of 8-OHdG.
ARTICLES
Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles
Research Team for Health Effects of Air Pollutants, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
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