The effect of study type on body weight and tumor incidence in B6C3F1 mice fed the NTP-2000 diet

Conestoga-Rovers & Associates, Rochester, NY 14650-2136, USA.
Toxicology mechanisms and methods (Impact Factor: 1.52). 03/2012; 22(6):466-75. DOI: 10.3109/15376516.2012.672482
Source: PubMed


The B6C3F1 mouse is the standard mouse strain used in National Toxicology Program (NTP) carcinogenesis studies. Over time, increased liver tumorigenesis that was correlated with elevated body weights was noted in males and females. NTP therefore replaced the NIH-07 diet with the NTP-2000 diet and returned to group housing of females as lower body weights were noted in group housed mice. However, recent studies reported study-type differences in body weights at 3 months using the NTP-2000 diet with higher weights evident in drinking water and inhalation studies compared to feed studies. Therefore, body weight and tumor incidence data were collected for untreated control mice from all 2-year NTP feed (12), drinking water (8), water gavage (6) and inhalation (10) studies that used the NTP-2000 diet in order to assess the impact of study type on body weights and tumor incidences. Results show statistically significant elevated body weights and liver tumor incidences in males and females from drinking water, water gavage and inhalation studies compared to results from feed studies. Thus, the elevated body weights and liver tumorigenesis noted in mice using the NIH-07 diet were also evident using the NTP-2000 diet, which was introduced to address body weight elevations. Given the study-type dependent effects noted, these results emphasize the importance of carefully selecting historical control data for B6C3F1 mice. Moreover, because of the association between body weight and liver tumorigenesis, these results may have implications regarding dose-level selection for carcinogenicity studies involving B6C3F1 mice based on the maximum tolerated dose.

5 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Yellow discoloration often develops in rice kernels during post-harvest storage, due possibly to fungal activity. The present study examined the changes in nutrient composition taking place during yellowing of rice, and the effects of feeding rats and broiler chicks on a moderately yellow rice at 600 g/kg diet. Nitrogen content was found to be higher in rice grains that had become more yellow, only part of the increase being in non-protein-N; however, relative to crude protein (N x 6.25) the concentrations of lysine, methionine, cystine and arginine were lower. There were no significant differences between white and yellow rice in the food intake, weight gain and efficiency of food utilization (EFU) of rats and chicks when diets were formulated to contain similar nutrient concentrations, or the same basal ingredient composition. Diet pelleting increased food intake and weight gain in both animal species, but reduced dry matter and energy digestibility in rats; effects on nutrient retention in chicks were largely non-significant. Liver weights of rats and chicks and pancreas weights of chicks were unaffected by yellow rice; however, chicks fed on mash had a larger pancreas on average than those fed on pellets. Thus, whilst the nutrient composition of rice is altered during yellowing, a moderately yellow rice is unlikely to produce major adverse effects when fed to rats and broiler chicks.
    British Journal Of Nutrition 12/1992; 68(3):573-82. DOI:10.1079/BJN19920116 · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diet is one of the most important environmental factors influencing growth, body weight, survival, and age-related diseases of rodents in chronic studies. NIH-07 open formula diet was the selected diet for the NTP studies from 1980 to 1994. A new diet designated as NTP-2000 diet is the current diet for mice in the NTP studies beginning in 1994. This report is a summary of results of untreated control groups of B6C3F1 mice fed NTP-2000 or NIH-07 diet from several retrospective 2-year dosed-feed and inhalation studies for differences in growth, body weight, survival, and tumor incidences. The dosed-feed studies were conducted in 3 different facilities located in the United States, and all the inhalation studies were conducted in 1 facility. During dosed-feed studies, male and female mice housed in polycarbonate cages and fed the NTP-2000 diet had lower maximum body weights than those fed NIH-07 diet. However, during inhalation studies, mice housed in wire mesh cages and fed the NTP-2000 diet had higher maximum body weights than the mice fed NIH-07 diet. Survival was higher in groups fed NTP-2000 diet irrespective of sex, housing conditions, or body weight compared to the corresponding groups fed NIH-07 diet. Survival was higher in mice housed in polycarbonate cages irrespective of diet and sex compared to the respective sex and diet groups housed in wire mesh cages. During inhalation studies, survival of male and female mice fed NTP-2000 diet was higher than that of the groups fed NIH-07 diet, although the body weights of NTP-2000 diet groups were higher than those of the groups fed NIH-07 diet. When the NTP-2000 diet was used, male and female mice in dosed-feed studies and male mice in inhalation studies had markedly lower incidences of liver tumors than the corresponding groups fed NIH-07 diet. Significant decreases in the incidences of lung tumors were observed only in the male groups fed NTP-2000 diet during dosed-feed studies. These results suggest that body weight may not be the major contributing factor for mortality and liver tumors and that an interaction between diet and housing conditions appears to affect the growth, survival and tumor incidences of B6C3F1 mice.
    Toxicologic Pathology 03/2003; 31(2):243-50. DOI:10.1080/01926230390183742 · 2.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the early 1970s, the National Cancer Institute (NCI) and National Toxicology Program (NTP) have conducted carcinogenesis and toxicology studies on several hundred chemicals using the B6C3F1 mouse. A number of publications have examined growth, survival, and tumor incidence over time, including the impact of changes in housing and diet. However, no reports have been published to date examining the variation in organ weights over time, especially in light of reported body weight effects associated with housing and diet changes. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from 2-wk, 3-mo, and 15-mo NCI/NTP investigations with report dates through August 2010 in order to examine organ weight changes over time and by study type. Study data were grouped into 5-yr intervals by initiation date. Body weights in males increased over time except in 2-wk studies, while body weights in females rose through 1993 and remained constant or declined thereafter. Higher body weights were noted in individually housed mice, and in drinking water studies compared to feed or inhalation studies. Elevated organ weights were typically associated with increased body weights except that lower organ weights were evident as early as 2-wk on study with the introduction of the NTP-2000 diet in 1994. Relative organ weights decreased over time in males and females. Finally, organ weight coefficients of variation (standard deviation/mean) declined over time in 2-wk, 3-mo, and 15-mo studies, which may reflect improved data collection methods or reduced interlaboratory variability.
    Journal of Toxicology and Environmental Health Part A 02/2012; 75(3):148-69. DOI:10.1080/15287394.2012.625551 · 2.35 Impact Factor
Show more