Robert B. McGandy

Effect of dose rate on the induction of experimental lung cancer in hamsters by alpha radiation

The effect of dose rate on the induction of lung cancer in Syrian hamsters by 5.3 MeV alpha particles was examined by varying the number of weekly intratracheal instillations of carrier-free 210Po. By this technique, most of the radiation dose to the lungs was delivered over intervals ranging from 10 to 120 days. Protraction of exposure over 120 days was slightly more carcinogenic at lower total lung doses (24 rad), but slightly less carcinogenic at higher doses (240 rad), than exposure limited to a 10-day interval. No synergism was observed between very low radiation exposures (2.4 rad) and simultaneously administered benzo[a]pyrene. The carcinogenic effect of a single intratracheal instillation of 210Po in isotonic saline was markedly enhanced by subsequent weekly instillations of 0.2 ml of saline alone, emphasizing the importance of noncarcinogenic secondary factors in the expression of radiation-induced lung cancer.

Histochemical, light and electron microscopic study of polonium-210 induced peripheral tumors in hamster lungs: Evidence implicating the Clara cell as the cell of origin

Abstract Peripheral lung tumors induced in Syrian golden hamsters by intratracheally administered polonium-210 (210Po) are similar to the peripheral lung tumors induced in many species by a variety of carcinogens. In addition, they show many of the histopathological features observed in human bronchiolar-alveolar carcinomas. Serial sacrifice studies of hamsters exposed to multiple instillations of 210Po have been carried out to identify the cell of origin of these tumors. By means of thin, plastic (glycol methacrylate) sections, electron microscopy, and histochemistry, we conclude that the bronchiolar Clara cell is the probable cell of origin, and that this view is generally compatible with many of the reported cytological characteristics of the human tumor.

An institutional approach to the dietary regulation of blood cholesterol in adolescent males

Abstract This study presents in detail an acceptable effective approach to initiate dietary modification to lower serum cholesterol in institutionalized, nonmotivated adolescent males. In order to simulate the traditional school menu pattern, considerable use was made of specially prepared food items to replace the ordinary market counterparts. During the Modified Diet periods, dietary fat intake was estimated to decrease from 39 (baseline) to 33% (modified diet) of total calories; saturated fatty acids decreased from 15 to 10% of total calories; and polyunsaturated fatty acids increased from 3 to 10% of total calories. The ratio of polyunsaturated to saturated fatty acids rose from 0.2 in the baseline diets to 1.0 on the modified diets, and mean daily intake of dietary cholesterol was reduced from 540 to 300 mg, a decrease of about 44%. Initial mean serum cholesterol level was 178 mg/100 ml. This was decreased promptly by about 15% upon introduction of the Modified Diet and returned to baseline levels after a short midterm vacation period and again after the summer vacation. Thus, an interrelationship between diet and level of blood cholesterol does exist in males as early as the second decade of life. Recognition and alteration of this environmentally determined risk factor during the adolescent years may result in lessened atherosclerotic vascular disease in later life.

Influence of genetic strain on the induction of lung cancer in hamsters by alpha radiation

Abstract The response was studied of four inbred strains of Syrian hamsters to multiple intratracheal instillations of the alpha emitting radionuclide polonium-210 adsorbed onto hematite particles. Marked differences occurred among strains in their tolerance to the instillations. There also appeared to be significant differences in the tumor induction times, but the frequency of lung tumors was similar in the four strains-varying between 33% and 50%. The influence of genetic strain might well be more marked with chemical carcinogens in which mechanisms of activation or detoxification become important factors which come under genetic control.

Morphologic and histochemical characteristics of cell lines derived from hamster peripheral lung tumors

Abstract Intratracheal instillation of the alpha emitter polonium-210 (210Po) or benzo[a]pyrene induces peripheral lung tumors in Syrian hamsters which have a combined epidermoid and adenomatous morphology similar in appearance to human bronchiolar-alveolar carcinoma. Two permanent cell lines derived from such tumors have been studied in an attempt to determine the cell of origin of the original peripheral tumors. The ultrastructural and histochemical characteristics of both the cells and of cheek pouch tumors grown from HLAC-4 and HLAC-14 cells at various stages of passage in tissue culture in general support, but do not prove, our hypothesis that Clara cells found in the terminal and respiratory bronchioles are the cells of origin of the peripheral lung tumors induced in hamsters by these carcinogens.

Systemic absorption of polonium-210 inhaled in cigarette smoke.

The kinetics of the change in the concentration of polonium-210 in the peripheral blood of six cigarette smokers has been studied up to 89 days altar sudden complete cessation of smoking. Circulating polonium-210 levels declined an average of 14% after three to four days, and 20.5% after 11 to 14 days. The results indicate that a major fraction of the Isotope inhaled in cigarette smoke is absorbed directly into the blood stream.

Observations on the Role of Lipids in Serum-Induced Intravascular Thrombosis.∗

Summary (1) A method of producing serum-induced intravascular thrombi has been adapted to use in a convenient laboratory animal, the chicken. (2) Dose-response curves can be constructed and statistically compared. (3) The factors influencing the clotting rates are not all known, but alterations in serum lipids in the assay animals did not influence the results.

Experimental Respiratory Carcinogenesis: Interaction between Alpha Radiation and Benzo (a) pyrene in the Hamster

We have previously shown that a high incidence of lung cancer can be induced in hamsters by multiple intratracheal instillations of either benzo(a)pyrene (BaP) or polonium-210 (210Po). The present experiments have used low doses of these 2 carcinogens, singly and together, in simultaneous and sequential designs. In terms of unequivocal lung tumors, 15 weekly instillations of 210Po (total 0.05 µCi) and BaP (total 4.5 mg) given simultaneously on the same carrier particles induced twice the prevalence of lung tumors expected from the additive effect of either carcinogen alone. In a separate experiment, a single instillation of 0.04 µCi 210Po led to only 1 tumor in 139 animals (0.7%) in contrast to 23 tumors among 135 animals (17%) when it was followed 18 weeks later by 7 weekly instillations of BaP (total 2.1 mg). These results suggest synergistic action between alpha radiation and BaP in the induction of lung cancer.

Is Coronary Heart Disease Preventable

Coronary heart disease is a leading cause of death in the United States.Factors implicated in the disease process include heredity, sex, advancing age, blood lipids, hypertension, heavy cigarette smoking, obesity, lack of physical activity, and stress.Dietary control of blood lipids seems to offer the most practical means of large-scale primary prevention of this disease.