COMPARATIVE TUMORIGENICITY OF 1-NITROBENZO[A]PYRENES AND 3-NITROBENZO[A]PYRENES, AND 3,6-DINITROBENZO[A]PYRENES AND 1,6-DINITROBENZO[A]PYRENES IN F344 DUCRJ RATS/
K. Horikawa et al., COMPARATIVE TUMORIGENICITY OF 1-NITROBENZO[A]PYRENES AND 3-NITROBENZO[A]PYRENES, AND 3,6-DINITROBENZO[A]PYRENES AND 1,6-DINITROBENZO[A]PYRENES IN F344 DUCRJ RATS/, Toxicology letters, 98(1-2), 1998, pp. 51-58
Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1,
6- and 3,6-dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo
[a]BP (BP), are present in the environment. These derivatives are pote
nt mutagens for Salmonella tester strains and we have preliminarily re
ported them to be carcinogenic in F344/DuCrj rats. In this study, the
tumorigenic action of 1- and 3-NBP, 1,6- and 3,6-DNBP, and BP induced
by subcutaneous injection into rats was found to differ according to t
he NO2-substitution in the BP structure. The chemicals were suspended
in equal volumes of beeswax and tricaprylin, and rats were subcutaneou
sly injected with single doses of 500, 1000, and 2000 mu g for 1- and
3-NBP, and of 8, 40, 200, and 1000 mu g for 3,6- and 1,6-DNBP, and BP
as a positive control. 3,6-DNBP and BP induced tumors in a dose-depend
ent manner at the injection site. Rats given 1000 mu g of 3,6-DNBP (29
24 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate
of 70 and 800io, respectively, and those given a minimum dose of 23 nm
ol for 3,6-DNBP and 32 nmol for BP per rat developed tumors at a rate
of 4.8 and 18.2%, respectively. However, rats given 500 and 1000 mu g
of 1- and 3-NBP did not develop any tumors while those given a high do
se, 2000 mu g, of each chemical developed tumors at only one of ten an
imals used. It was concluded, therefore, that these chemicals are weak
carcinogens. Histologically, most of the tumors were malignant fibrou
s histiocytomas. Rats given various doses of 1,6-DNBP did not develop
any tumors at the injection site. The failure of 1,6-DNBP to induce tu
mors may involve its metabolites because of the lower mutagenicity of
its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is sugge
sted, therefore, that tumorigenicities of NBPs and DNBPs differ accord
ing to the NO2-substitution on the chemical structure, which may be du
e to the possible nitroreduction of the chemicals. (C) 1998 Elsevier S
cience Ireland Ltd. All rights reserved.