Flavor-cued modulation of intake in rats: role of familiarity and impact on 24-h intake.

Following training with distinctively flavored nutritive solutions that differ in concentration and thus in caloric value, rats demonstrate flavor-postingestive consequence learning by preferentially consuming one of the flavors in two-bottle tests (both flavors in nutrient-identical solutions.) Experiment 1 investigated whether the relative familiarity of the flavor-nutrient combinations encountered in two-bottle tests contributes to the observed preference. One of the training concentrations (rather than the customary intermediate concentration) was used to present the flavors in testing; thus, one of the flavors was in a familiar context while the other was in an unfamiliar context. The results of two independent trials (rats trained with 1 and 5% sucrose; rats trained with 5 and 40% sucrose) confirmed that two-bottle test preference was not a preference for the familiar flavor-nutrient combination. Experiment 2 examined whether caloric expectancies based upon a previously learned flavor-postingestive consequence association would affect total daily intake. On alternating days, rats consumed 30 mL of dilute (5%) and concentrated (40%) sucrose, each distinctively flavored. When given 30 mL of 22.5% sucrose containing each of the flavors on separate test days, they ate less chow and thus fewer total calories over 24 h when given the flavor previously paired with concentrated sucrose. Experiment 3 replicated the design of Experiment 2 except that fat calories were used instead of sucrose; no significant adjustment of chow intake in extinction tests was noted, even when the number of fat calories used in training was increased (Experiment 4). Thus, rats did not exhibit flavor-cued modulation of chow intake when trained with fat, in contrast to responsivity to flavor cues when trained with sucrose. This differential responding to fat versus carbohydrate calories is consistent with previous observations, in a variety of paradigms, that modulation of caloric intake is less energetically appropriate when ingested foods are high in fat relative to high-carbohydrate foods.     

Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking.

The factors that determine progression of cervical intraepithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is an independent risk factor for cervical neoplasia, suggesting that polymorphism at detoxicating enzyme loci such as cytochrome P450 CYP2D6 and glutathione S-transferase GSTM1 may determine susceptibility to these cancers. We have studied the frequencies of genotypes at these loci in women suffering low-grade CIN, high-grade CIN and SCC. A non-cancer control group was provided by women with normal cervical histology suffering menorrhagia. Comparison of the frequency distributions of the CYP2D6 PM, HET and EM genotypes (G-->A transition at intron 3/exon 4 and base pair deletion in exon 5) revealed no significant differences between the menorrhagia and SCC groups. Frequency distributions in the menorrhagia group, however, were significantly different (P < 0.04) from those in the low- and high-grade CIN groups. Thus, the proportion of EM was significantly larger (P < 0.03) and of HET generally lower. We found that the frequency of GSTM1 null in the menorrhagia and case groups was not significantly different. Interactive effects of enzyme genotypes with cigarette smoking were studied by comparing the multinomial frequency distributions of CYP2D6 EM/GSTM1 null/smoking over mutually exclusive categories. These showed no significant differences between the menorrhagia group and SCC or low-grade CIN groups. The frequency distribution in high-grade CIN, however, was significantly different to that in the menorrhagia group and in both SCC and low-grade CIN groups. This study was identified, for the first time, an inherited characteristic in women with high-grade CIN who appear to be at reduced risk of SCC. Thus, women with CYP2D6 EM who smoke have increased susceptibility to high-grade CIN but are less likely to progress to SCC, possibly because they effectively detoxify an unidentified chemical involved in mediating disease progression.