Immunotoxicological Evaluation of Genetically Modified Rice Expressing Cry1Ab/Ac Protein (TT51-1) by a 6-Month Feeding Study on Cynomolgus Monkeys.
The present study was performed to evaluate the food safety of TT51-1, a new type of genetically modified rice that expresses the Cry1Ab/Ac protein (Bt toxin) and is highly resistant to most lepidopteran pests. Sixteen male and 16 female cynomolgus monkeys were randomly divided into four groups: conventional rice (non-genetically modified rice, non-GM rice), positive control, 17.5% genetically modified rice (GM rice) and 70% GM rice. Monkeys in the non-GM rice, positive control, and GM rice groups were fed on diets containing 70% non-GM rice, 17.5% GM rice or 70% GM rice, respectively, for 182 days, whereas animals in the positive group were intravenously injected with cyclophosphamide every other day for a total of four injections before the last treatment. Six months of treatment did not yield abnormal observations. Specifically, the following parameters did not significantly differ between the non-GM rice group and GM rice groups: body weight, food consumption, electrocardiogram, hematology, immuno-phenotyping of lymphocytes in the peripheral blood, mitogen-induced peripheral blood lymphocyte proliferation, splenocyte proliferation, KLH-T cell-dependent antibody response, organ weights and ratios, and histological appearance (p>0.05). Animals from the GM rice group differed from animals in the non-GM rice group (p<0.05) in several parameters: specifically, their body temperatures and serum alanine aminotransferase (ALT) levels were higher, whereas their levels of serum K+, Cl- and cytokines (IL-2, IL-4 and IL-5) were lower. Because dose- or time-dependent changes were not observed in this study and animals appeared histologically normal, the aforementioned differences were not considered to be adverse or related to the treatment with GM rice. In conclusion, a 6-month feeding study of TT51-1 did not show adverse immunotoxicological effects on cynomolgus monkeys.
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.|Center of Safety Evaluation on New Drug, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
Xiaoyan
X
Tan
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Xiaobing
X
Zhou
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Yao
Y
Tang
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Jianjun
J
Lv
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Lin
L
Zhang
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Li
L
Sun
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Yanwei
Y
Yang
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Yufa
Y
Miao
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Hua
H
Jiang
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.|Center of Safety Evaluation on New Drug, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
Gaofeng
G
Chen
Center of Safety Evaluation on New Drug, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
Zhiying
Z
Huang
Key Laboratory of Beijing for Safety Evaluation of Drugs, National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing, People's Republic of China.|Center of Safety Evaluation on New Drug, School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
Xue
X
Wang
IUBMB Life. 2012 Mar;64(3):242-50
22215564
Food Chem Toxicol. 2014 Mar;65:312-20
24309144
J Fish Dis. 2007 Apr;30(4):201-12
17394522
Toxicology. 2008 Mar 12;245(1-2):24-34
18215453
J Agric Food Chem. 2008 Dec 10;56(23):11533-9
19007233
Food Chem Toxicol. 2007 Mar;45(3):339-49
17050059
Methods Mol Biol. 2010;598:159-71
19967512
Transgenic Res. 2015 Apr;24(2):295-308
25367203
Fundam Appl Toxicol. 1992 Feb;18(2):200-10
1534777
J Sci Food Agric. 2011 Aug 30;91(11):2066-72
21520451
J Immunotoxicol. 2005 Oct 1;2(4):191-6
18958673
Food Chem Toxicol. 2013 Dec;62:390-6
24012644
Methods Mol Biol. 2010;598:341-59
19967524
PLoS One. 2012;7(12):e52507
23300690
PLoS One. 2014 Feb 10;9(2):e78566
24520311