Effects of chronic exposure to sublethal concentrations of lead acetate on heme synthesis and immune function in red-tailed hawks.

Red-tailed hawks were exposed to sublethal levels of lead acetate for periods of 3 or 11 weeks. Alterations in the heme biosynthetic pathway were demonstrated after the first week of exposure to 0.82 mg lead per kilogram body weight per day. Activity of erythrocyte porphobilinogen synthase (aminolevulinic acid dehydratase) was depressed significantly and did not return to normal levels until 5 weeks after the termination of lead treatments. A rapid and relatively brief increase in erythrocyte free protoporphyrin and a slower but more prolonged increase in its zinc complex were also demonstrated with exposure to this dose of lead for 3 weeks. Less substantial decreases in hematocrit and hemoglobin levels occurred but only in the longer experiment with exposure to higher lead levels. Short term, low level lead exposure did not effect immune function significantly in the hawks, as measured by antibody titers to foreign red blood cells or by the mitogenic stimulation of T-lymphocytes. Increased lead exposure produced a significant decrease in the mitogenic response but had no effect on antibody titers.

Effect of sublethal lead exposure on gastric motility of red-tailed hawks.

In order to determine the effects of low level lead exposure on gastric motility in raptors, strain gage transducers were surgically implanted on the serosal surface of the muscular stomach of three red-tailed hawks. The frequency and amplitude of gastric contractions during ingestion and early digestion were monitored for 1 week under control conditions and for 3 weeks while the birds were fed 0.82 or 1.64 mg lead (as lead acetate) per kg body weight each day. Exposure to these doses did not appreciably affect either the frequency or amplitude of gastric contractions in these birds. This low level lead exposure also had no consistent effect on the regular egestion of pellets of undigested material by hawks. Daily exposure to doses up to 6.55 mg lead/kg body weight did not affect the frequency or timing of pellet egestion, and exposure to 1.64 mg lead/kg did not affect the gastric contractions associated with pellet egestion. Although gastrointestinal dysfunction is often associated with clinical cases of acute lead toxicity, chronic exposure to these low levels of lead acetate did not significantly alter gastric motility in red-tailed hawks.

Acid phosphatase activity of chondroclasts from Fusarium-induced tibial dyschondroplastic cartilage.

Tibial dyschondroplasia was induced in broiler chickens by oral administration of fusarochromanone, the toxic component of Fusarium equiseti. In two experiments, the activity of acid phosphatase in chondroclasts was assessed histochemically. Chicks were examined at 7, 14, 21, and 28 days of treatment in Expt. 1 and at 2, 4, and 6 days of treatment in Expt. 2. The staining for acid phosphatase was consistently lower in fusarochromanone-treated chicks after 2 days of treatment than in age-matched controls, and the onset of this difference corresponded to the onset of lesions. However, the decrease in acid phosphatase staining intensity was significant only at day 21 in Expt. 1 and at day 6 in Expt. 2. The deficiency of acid phosphatase in chondroclasts was judged to be of insufficient magnitude to account for the accumulation of growth plate cartilage that characterizes tibial dyschondroplasia.

The immune basis of dosage-induced reversal of the rank-order of strain susceptibility to MCA.

Even AHH-inducible mouse strains vary in their susceptibilities to MCA sarcomagenesis. Previous work showed that the rank-order of strain susceptibility depended upon the dosage of MCA; the strain most susceptible to a high dose became the least susceptible to a low one and vice versa. We now confirm our previous findings and test the hypothesis that the reversal, with dosage, of the rank-order of relative strain-susceptibility has an immunological basis. This was tested in two ways: by examining the effect of immunosuppression on strain-susceptibility to sarcomagenesis and by transplanting parental bone marrow into irradiated F1 hybrid to see if the relative MCA-susceptibility characteristics of the parental donors could be transferred. The results of both studies suggest that the rank-order-reversal phenomenon is caused, at least in part, by differences in the immunological reactivities of the strains. Inasmuch as immunosuppression inhibited the response of the C3 mice to a high dose of carcinogen, but facilitated carcinogenesis among the B6, the level of innate immune capacity most conducive to high-dose carcinogenesis is apparently intermediate between the levels of these two strains.

Morphogenesis of Fusarium sp-induced tibial dyschondroplasia in chickens.

Tibial dyschondroplasia was induced in female broiler chicks by the incorporation of 2% Fusarium roseum "Alaska" culture into their starter ration. Chicks were placed on this diet at one day of age and maintained until they were killed at four days or one week. Proximal tibial physes were grossly thickened into cone-shaped masses of cartilage by one week of age. Microscopically, lesions were in both ages of treated chickens and were characterized by thickening of the transitional zone which was especially prominent in the center of the growth plate. This zone was unmineralized, avascular, and contained chondrocytes which were crenated and densely eosinophilic. The cartilage matrix was pale and contained some patchy eosinophilic foci. Four growth plates with tibial dyschondroplasia and four normal growth plates from each of the four-day and one-week-old age groups were evaluated based on the following parameters: number of metaphyseal vascular sprouts, distance between the proliferative/transitional junction and the tip of the metaphyseal vascular sprouts, width of the tips of the metaphyseal sprouts, distance between tips of adjacent metaphyseal vascular sprouts, and number of perforating vessels in the proliferative zone. The distance between the proliferative/transitional junction and the metaphyseal sprout tips was greatly increased (p less than 0.01) in the affected four-day and one-week-old chickens compared to age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Chondroclasts in fusarium-induced tibial dyschondroplasia. A histomorphometric study.

The role of chondroclasts in the pathogenesis of Fusarium roseum-induced tibial dyschondroplasia (TD) was examined in a histomorphometric study. TD developed rapidly in broiler chickens placed at 1 day of age on rations containing either 3% (Experiment 1) or 2% (Experiment 2) F roseum cultures. In Experiment 1 the frequency of TD in birds killed at 4 weeks of age was 90%. In Experiment 2, birds were killed at intervals from 4 days until 4 weeks of age. By 1 week of age, 70% of birds examined had characteristic accumulations of prehypertrophic cartilage at the proximal tibial physis, and the frequency of TD in 4-week-old birds was 80%. Sections of hypertrophic cartilage from F roseum-fed and control birds from both experiments were examined for determination of the volume density of chondroclasts along the vascular channel boundary. Chondroclast density was consistently lower in F roseum-fed than in control birds, but the difference was significant only at 4 weeks of age. The fact that gross lesions were evident before a significant decrease in chondroclast density occurred indicates that a decrease in the density of chondroclasts was not an essential factor in the accumulation of cartilage characteristic of TD.

Significance of three-dimensional growth patterns of mammary tissues in collagen gels.

Five tumor cell lines that originated from a single mouse mammary adenocarcinoma, normal mammary tissue, a preneoplastic alveolar nodule line, and a tumor developing spontaneously from that preneoplastic line were used to study the different three-dimensional growth patterns that mammary tissues produce in collagen gel. We describe five different outgrowth morphologies, one of which may represent normal stromal tissue and infiltrating cells. One type was produced both by tumors and by normal mammary gland tissue in an age-related fashion, i.e. more outgrowths of this type were produced by mammary tissue from older mice. The outgrowth patterns for the tumor cell lines were not related to morphology in monolayer culture. Certain of the tumor lines, including one variant-producing line, produced multiple outgrowth patterns. Our results indicate that this cultivation technique may be a useful method for studying the heterogeneity of mammary tumors and may facilitate the isolation of mammary tumor subpopulations.

Influence of immune status of host on immunogenicity of tumors induced with two doses of methylcholanthrene.

Previous studies by Prehn demonstrated a direct correlation between the dose of carcinogen used for tumor induction and the immunogenicity of the resulting tumors. The purpose of the present study was to determine the role of the host's immune response and the influence of the carcinogen on immune function in this relationship. For that reason, a comparison was made of the immunogenicities of tumors induced with two doses of carcinogen in immunologically normal mice and in mice immunodepressed by adult thymectomy and irradiation. If the direct relationship between dose and immunogenicity demonstrated in normal mice was due to the degree of immunosuppression produced by the carcinogen, this correlation should not be apparent in mice already immunosuppressed. Although there was some increase in the immunogenicity of tumors induced in the immunosuppressed mice, the same relationship between carcinogen dose and immunogenicity was observed in both groups of mice. These results indicate that the degree of immunogenicity of tumors induced with both high and low doses of carcinogen was influenced by immunoselection, but in addition another, non-immunologic factor was significant in the relationship between carcinogen dose and immunogenicity.

Macrophage content and immunogenicity of C57BL/6J and BALB/cByJ methylcholanthrene-induced sarcomas.

A total of 33 methylcholanthrene-induced sarcomas, growing in C57BL/6J or BALB/cByJ mice, were tested for their immunogenicity and for their relative macrophage content. No relationship was demonstrated between these two characteristics. These results suggest that the direct correlation between macrophage content and immunogenicity demonstrated in rat tumor model systems may not hold for other systems.

Rank order of sarcoma susceptibility among mouse strains reverses with low concentrations of carcinogen.

Ten mouse strains in which aryl hydrocarbon hydroxylase can be induced, or F1 hybrids of these strains, were ranked according to their sarcoma susceptibility when exposed to a high concentration (5 percent) of the chemical carcinogen 3-methylcholanthrene. This rank order was reversed when the concentration of 3-methylcholanthrene was reduced to 0.05 percent.