[Effect of 7,12-dimethylbenz(a)athrancene on immune function in metallothionein gene-knocked-out mice].
OBJECTIVE
To study the immunotoxicity induced by 9,10-dimethyl-1,2-benzathrancene (DMBA) in metallothionein gene-knocked-out mice [MT(-/-)] as compared with that in wild-type mice [(MT(+/+)].


METHODS
Female mice were treated with 25 mg/kg and 50 mg/kg of DMBA i.p., respectively and immunized with sheep red blood cells (SRBC) i.v. on the following day and rechallenged by injection of SRBC via footpad s.c. on the fourth day post-immunization. Humoral and cell-mediated immune function was assessed by the number of spleen IgM antibody plaque formation cells (PFC) to SRBC and cell-mediated delayed-type hypersensitivity (DTH) measured by footpad swelling thickness.


RESULTS
After treatment with 25 mg/kg DMBA, a decrease in weight of their spleen and thymus and PFC/spleen were observed in MT(-/-) mice, while only decrease in thymus weight of MT(+/+) mice. The humoral function was suppressed by 72% in MT(-/-) mice. No obvious change in cell-mediated immune function was observed both in MT(-/-) and MT(+/+) mice. Both humoral and cell-mediated immune function were suppressed more severe (91%) in MT(-/-) mice treated with 50 mg/kg DMBA than those treated with 25 mg/kg DMBA (72%). DTH was not altered by DMBA in MT(+/+) mice. The weight of their spleen and thymus decreased and humoral immune function suppressed in MT(+/+) mice, but these changes were significantly less severe. No obvious suppression of cell-mediated immune function was observed in MT(+/+) mice.


CONCLUSIONS
Their humoral and cell-mediated immune function was more susceptible to being suppressed by DMBA in MT(-/-) mice, indicating that MT could protect their immune function from damage caused by DMBA.
Lei
Zhiming
Z
Department of Toxicology, School of Public Health, Peking University, Beijing 100083, China.
Ruan
Ming
M
Qiu
Feichan
F
Wei
Xuetao
X
Li
Xueting
X
Jia
Fenglan
F
Shang
Lanqin
L
Zhang
Baoxu
B
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D007109:Immunity / Q000187:drug effects*; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects
D015127:9,10-Dimethyl-1,2-benzanthracene; D008668:Metallothionein