Dr. Germolec et al., INDUCTION OF CYP1A1 AND ALDH-3 IN LYMPHOID-TISSUES FROM FISHER-344 RATS EXPOSED TO 2,3,7,8-TETRACHLORODIBENZODIOXIN (TCDD), Toxicology and applied pharmacology, 137(1), 1996, pp. 57-66
The immune system is a primary target for toxic insult by a number of
drugs and environmental chemicals, many of which require activation to
toxic metabolites by drug-metabolizing enzymes. We compared the induc
tion of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1
A1) and aldehyde dehydrogenase (ALDH), in lymphoid tissues of F344 rat
s following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
ALDH was induced in both the spleen and the thymus after TCDD treatme
nt, with maximal expression at 9 and 15 days, respectively. Thymic mic
rosomal preparations from TCDD-treated animals expressed elevated leve
ls of inducible CYP1A1 as compared to microsomes from the spleens of t
reated animals or tissues from control rats. TCDD treatment also resul
ted in increased ethoxyresorufin-O-deethylase (EROD) activity in the t
hymus. There were no detectable mRNA transcripts for CYP1A1 in periphe
ral blood or splenic lymphocytes from treated animals; however, CYP1A1
transcripts were induced in isolated thymocytes, whole spleen, and wh
ole thymus. In vitro exposure to TCDD did not result in induction of i
mmunoreactive CYP1A1 in thymocytes unless simultaneously activated wit
h the mitogen, phytohemagluttinin (PHA). Immunohistochemical localizat
ion of CYP1A1 in immune tissues indicated that cells other than the ly
mphoid populations are responsible for the increased CYP1A1 expression
. The pattern of CYP1A1 induction was related to the expression of the
Ah receptor (AhR) in immune tissues. Western blot analyses demonstrat
ed less AhR present in peripheral blood lymphoid cells and spleen, as
compared to whole tissues. These studies indicate that while drug-meta
bolizing enzymes are present in immune tissues, the induction of enzym
es is selective in different lymphoid cells. (C) 1996 Academic Press,
Inc.