The hypothesis that the month-specific rate of return to ovarian cyclicity after childbirth is causally related to suckling pattern was tested for a population of New Mexican women recruited within the service area of New Mexico Highlands University and for a nationwide USA subpopulation of women recruited through membership of the Couple to Couple League (CCL). Survival analysis for time-dependent covariates was used, and significant predictors of the first postpartum menses were found. Important differences were detected in the suckling pattern for the two groups and a 5:2 differential was found in their respective rates of menstrual cycle recovery. Although the two groups were comparable perinatally, daily and time-windowed breast-feeding performance fell off at twice the rate for the New Mexico population when contrasted with the CCL sample. For both populations, the introduction of solid feeds was a strong and significant predictor of returning menstrual cyclicity, independent of suckling pattern.

Dysfunction in homeostatic mechanisms of cell death and proliferation are considered to be important in the pathogenesis of chemically induced neoplasia. p53 has been implicated in the regulation of cell death and proliferation. To determine whether expression of apoptosis, proliferating cell nuclear antigen (PCNA), and p53 differ between an alkylating agent and a polycyclic aromatic hydrocarbon, host response was measured through sequential immunohistochemical detection of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method), PCNA PC-10, and p53 (PAb 240) in livers of the fish Fundulus grandis. Nine hundred fish were randomly assigned to 3 groups of 300 fish each and kept in separate aquarium tanks. One group of fish was exposed to 6.7 μM N -methyl-N' -nitro-N -nitrosoguanidine (MNNG), 1 group was exposed to 6.9 mM 2-aminofluorene (2-AF), and the remaining group served as a control. A significant decrease (p = 0.005) in the level of apoptosis and a significant increase (p < 0.0001) in the level of p53 were found on experimental day 180 in the livers of MNNG-exposed fish. PCNA was significantly increased (p < 0.005) by day 9 of the experiment in both MNNG and 2-AF fish when compared with controls, but no significant differences existed between the 2 groups of treated fish. Response of fish liver cells to MNNG-mediated and 2-AF-mediated injury differs, at least initially, in the expression of p53, inhibition of apoptosis, and increased net cell proliferation. Concurrent use of a marker for cell death with a marker of proliferation greatly enhances the assessment of the effect of these compounds on liver cells.

Three oxygenated N-nitrosopiperidines--nitroso-3-piperidinol, nitroso-4-piperidinol, and nitroso-4-piperidone--were prepared and given in drinking water at equivalent molar doses to Sprague-Dawley rats. All were potent carcinogens, 100% of the rats developed tumors in all treatment groups. Nitroso-3-piperidinol resembled nitrosopiperidine in inducing a high incidence of tumors of the nasal cavity and upper alimentary tract, and a few liver tumors. Nitroso-4-piperidinol and nitroso-4-piperidone caused a high incidence of tumors of the nasal cavity but very few tumors of the upper alimentary tract. After treatment with the 4-substituted compounds, a high incidence of liver tumors was observed in females but not in males.

Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one-half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination.

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