Neal K. Clapp

Effects of wheat, rice, corn, and soybean bran on 1,2‐dimethylhydrazine‐induced large bowel tumorigenesis in F344 rats

This study was designed to determine the relative effects of four dietary brans on large bowel tumorigenesis in rats treated with 1,2-dimethylhydrazine (DMH). Four-week-old F344 rats were fed a 20% bran (either wheat, rice, corn, or soybean) semisynthetic diet or a no-fiber-added control diet for life. All rats except for one control diet for life. All rats except for one control group were infected with DMH (2SC doses; approximately 150 mg/kg body weight) at 8 and 10 weeks of age. Two additional groups were fed the control diet and then at 4 and 18 weeks, respectively, after the second DMH dose, were fed the wheat bran diet. All surviving rats were killed 9 months following the first DMH dose. Survival was increased in all groups receiving bran diets. Large bowel tumor incidences in the DMH group were as follows: control, 95%; wheat, 75%; rice 86%; corn, 100%; soybean, 84%; wheat after 4 weeks, 62% (lower than control group, p less than 0.05); wheat after 18 weeks, 84%. All but one of the DMH groups had approximately two tumors/tumor-positive rat; the corn group had four. The effect of bran on large bowel carcinogenesis appears to depend both on the source of bran and when it is fed in relation to tumor initiation.

interactions of ionizing radiation, nitrosamines, sulfonoxyalkanes and antioxidants as they affect carcinogenesis and survival in mice.

Butylated hydroxytoluene (BHT), pretreatment of 8-wk-old BALB/c mice for 28 days protected against 30-day lethality by X-rays, diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulfonate (EMS) but not against methyl methanesulfonate (MMS). In X-ray survivors, neither mean survival nor leukemia incidences were affected by BHT. However, BHT (lifetime), given alone or with DEN (300 MG/KG BW in H2O) or 250 R X-rays, increased irradiated survivors at 18 months but not leukemia or tumor incidences. BHT + DEN treated females had increased survival and a decreased frequency of forestomach squamous carcinomas compared with DEN alone; no differences were seen in males or in pulmonary adenomas. In X-ray + DEN treated females, effect upon survival was additive, but the specific diseases causing this effect were not identified.

A positive correlation between declining immune competence and early mortality associated with diethylnitrosamine carcinogenesis in aging mice

The effect of age (2.5, 9.5, and 17 months) at time of treatment upon diethylnitrosamine (DEN) carcinogenesis and immune competence has been assessed in female BALB/c mice. Median times of death were 193, 168, and 125 days, respectively, after termination of DEN treatment. Immune competence as a measure by both cell-mediated and humoral immune parameters immediately after DEN treatment was not significantly different among treated and age-matched non-treated control animals. In contrast, a significant age-related decline in immune competence was seen in both DEN-treated and non-treated controls, thereby demonstrating a direct and positive correlation between the natural age-related decrease in immune competence and cancer-induced advanced mortality.

Anti-colitic efficacy of SC-41930 in colitic cotton-top tamarins

To evaluate anti-colitic efficacy, eight cotton-top tamarins (CTTs) with histologically confirmed persistent active colitis were given the anti-inflammatory agent SC-41930 (10 mg/kg BW by gavage BID) for eight weeks. Colonic endoscopy and biopsy observations, CBCs and clinical chemistries, and stool consistency were evaluated pre-, mid-, and posttreatment. Colitic activity was graded histologically from A1 (mild) to A5 (severe); results varied among the seven animals that completed the study: five improved, one worsened, and one was unchanged. Serum enzyme levels were significantly reduced with treatment. Stool condition remained puddly throughout treatment and body weights did not vary from pretreatment levels. However, SC-41930 produced histological evidence (reduced numbers of polymorphonuclear cells) of anti-colitic efficacy over an eight-week treatment period in CTTs with persistent active colitis. These results support the use of the CTT colitis model to evaluate efficacy of therapeutic agents and provide useful predictive information to aid in the medical management of human IBD.

Qualitative alterations in plasma esterases in BALB/c mice following the administration of diethylnitrosamine☆

Selected non-specific plasma esterases in female BALB/c mice, separated by polyacrylamide gel electrophoresis, were qualitatively altered following treatment of the mice with diethylnitrosamine (DEN). These alterations include a decreased preference for naphthyl butyrate as a substrate relative to naphthyl acetate; decreased sensitivity to enhancement by divalent cations such as Ca2+, Mg2+, and Mn2; and an increased sensitivity to inhibition by eserine. All esterase species affected were also quantitatively altered and some were testosterone-dependent.