Alt. Spinardi-barbisan et al., Lymphoproliferative response and T lymphocyte subsets in a medium-term multi-organ bioassay for carcinogenesis in Wistar rats, CANCER LETT, 154(2), 2000, pp. 121-129
The lymphoproliferative response and T lymphocyte subsets were evaluated at
different stages of carcinogenesis in male Wistar, rats sequentially initi
ated with N-diethylnitrosamine (DEN), N-butyl-N-4(hydroxybutyl)nitrosamine
(BBN), N-methyl-N-nitrosourea (MNU), dihydroxy-di-N-propylnitrosamine (DHPN
) and N,N'-dimethylhydrazine (DMH) (DMBDD initiation). One group was evalua
ted at the 4th week and other initiated group at the 30th week. Two initiat
ed groups were also exposed through diet to 7-acetylaminofluorene (2-AAF) o
r phenobarbital (PB), from the 6th until the 30th week. Two groups received
only 2-AAF or PB until the 30th week. Five groups were studied to evaluate
the effects of each initiator. The lymphoproliferative response was induce
d in vitro by concanavalin A and the percentage of T lymphocyte subsets was
determined by flow cytometry, All groups submitted to initiation only, ini
tiation plus promotion, or promotion only, developed significantly more pre
neoplastic: lesions than the untreated control group. The main target organ
s for tumor development were the liver, colon, urinary bladder, kidneys and
Zymbal glands, mainly in the group treated with DMBDD + 2-AAF, There were
no alterations of the lymphoproliferative response and of the T lymphocyte
subsets percentage in the DMBDD-treated group at the 4th and 30th weeks. At
the 30th week, the T lymphocyte subsets percentage was also not affected i
n the initiated groups after treatments with 2-AAF or PB. The lymphoprolife
rative response, however, was decreased in the DMBDD + 2-AAF group and in t
he groups treated only with 2-AAF or PB, The present results indicate that
the initiating chemicals used in the DMBDD initiation protocol do not exert
any influence on the immune system. The alteration of lymphoproliferative
response induced at the advanced stage of carcinogenesis without alteration
of T lymphocyte subsets may indicate that the influence of 2-AAF and PB on
the immune system is functional and not toxic. (C) 2000 Elsevier Science I
reland Ltd. All rights reserved.