主题：《国际生物学报》：转基因玉米对雄鼠的肾脏尺寸影响最大 -- 思想的行者

We have previously reported indications of toxicity in rats fed with MON 863 GM maize for 90 days [5]. However, these signs of toxicity alone do not constitute proof of adverse health effects. We have extended our initial analysis on the MON 863 feeding data by collectively compiling the significant differences observed in the physiological and biochemical parameters measured in feeding trials of rats with each of the three GM maize varieties MON 863, MON 810 and NK 603 (Tables 1, 2; Annex Table E). When we then initially compare all p-values in our calculations with those of Monsanto (significant and non significant differences, Annex Table E), we obtain ratios of 432/452 (NK 603), 435/450 (MON 810) and 442/470 (MON 863). By employing our statistical methods even if we reached a concordance with Monsanto's results (Annex Table E), the level of precision of the main effects and their interpretation are highly different. Therefore, we then progressed to consider only relative differences over 5% (Tables 1 and 2).

.1. NK 603

We first evaluated the results for the NK 603 feeding trials. The observations shown in Table 1 with relative differences versus controls reveal that of 23 significantly different effects that are supposed to be due to this GM maize, 18 are in males (raw means with SEM; Annex Table F). The repartition of effects is thus sex-dependent. In addition, in general liver (Fig. 1) and kidney (Fig. 2) parameters in all rats are sex differentially expressed. This is evident not only in the experiments involving NK 603, independently of the treatment at week 14, but also at week 5 (data not shown), but similarly observed in the MON 810 and MON 863 feeding tests (Annex Fig. A- Fig. D).

Males are clearly more sensitive than female animals to show physiological disturbances when fed NK 603. This is not observed for all three GM maize varieties. Moreover, most effects appear to be dose-dependent since 83% of male effects emerge only at the 33% feeding level (15/18), the highest GM maize concentration in the diet (Table 1). The maximal mean differences are observed in male kidney parameters.

Urine phosphorus, for instance, is importantly disturbed in a dose-dependent manner and at both 5 and 14 week periods of feeding and hence reproducible over time. The significant effect at this level does not appear to be a false positive result (week 5, 33%, adjusted p<0.003 for FDR calculated according to Benjamini and Yekutieli), considering that all parameters were not independent. Comparable results were also obtained for relative lymphocyte and neutrophil differences (all for males, week 14, 33%, adjusted p<0.005).

3.3. MON 863

We have already described our evaluation of the MON 863 rat feeding studies [5]. Sex-dependency is well marked in this case also for the spreading of all parameters in liver and kidney (Annex Fig. C & Fig. D). The 34 significant GM-linked effects are equally distributed among males (16) and females (18). This contrasts with what is observed with NK 603 and MON 810. Nevertheless, 9/16 (56%) of males show statistically significant differences in kidney compared to 4/18 females. However, although kidney parameters represent only 37.5% of all measurements, these data show a male-specific effect in kidney function. This trend is somewhat opposite to what is seen in liver parameters where males showed significant effects in 5/16 cases whereas the rate is 9/18 in females. Male rats also appear more sensitive to kidney disturbances at the higher GM feeding dose (11 effects at 33% versus 5 at 11%).

Additional statistically significant differences include (i) a serum glucose and triglyceride increase (up to 40%) in females versus controls, together with a higher liver (7%) and overall body (3.7%) weight, (ii) elevated creatinine, blood urea nitrogen and urine chloride excretion in females, but greater variation in male kidney function (creatinine, and in urine sodium, potassium and phosphorus), (iii) up to a significant kidney weight decrease (7%) with a noticeable chronic nephropathy in males [18], (iv) a decrease (3.3%) in male body weights and (v) some liver function differences in males (albumin, globulin, as in females, plus alanine aminotransferase), although none of the FDR-adjusted p-values are significant.

Furthermore, we have also measured in this study for the first time the differences between time-related variations (at weeks 5 and 14) for this GM maize variety, at each feeding dose versus controls. We have represented these variations for each rat for all parameters. Among these, the significant variations corresponding to disturbed parameters are illustrated (Figs. 4-7). Our analysis clearly shows that female rat triglyceride levels vary between 5 and 14 weeks of feeding (Fig. 4; p=0.025). Triglyceride levels increase over time within the GM maize feeding group and whilst decreasing in the case of controls. Again in females, the increase in creatinine caused by MON 863 is more evident with longer feeding periods at an 11% level (Fig. 5; p=0.022). Another significant difference (p=0.011), which we observe is a reciprocal variation in female urine chloride excretion (Fig. 6). In the males, only urine potassium decreases over time with the consumption of GM feed but increases in controls (Fig. 7, p=0.011).

In summary, the tendency for physiological disturbance is characteristic of almost all rats of all GM-fed treatment groups, and physio-pathological profiles differ according to dose or sex.