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Biomedical subjects

L M Anderson

Publications and source records attributed to L M Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1979

Induction of reproductive system tumors in mice by N6-(methylnitroso)-adenosine and a tumorigenic effect of its combined precursors.

Interaction of the naturally-occurring nucleoside, N6-methyl adenosine, with nitrite, a reaction that occurs readily under acidic conditions, results in the formation of a nitrosamine, N6-(methylnitroso) adenosine[m6(NO)Ado]. This nitrosamine was given in the drinking water (1 mM solution) of non-inbred Swiss mice from 3 weeks of age until death. It caused a significant increase in the incidence of primary lung tumors, compared with controls. It also induced reproductive tract tumors in 80% of the exposed females, including mammary tumors in 60% and uterine tumors in 25%. The precursors of m6(NO) Ado, m6Ado and nitrite, did not elevate tumor incidence when given singly, but when administered together resulted in a significant increase in numbers of lung tumors in the males. The nitrosamine base, N6-(methylnitroso)adenine, was found to be a less potent carcinogen than m6(NO)Ado, causing lung tumors only in males and possibly a few mammary tumors in females. These results indicate the in vivo formation of a carcinogen from m6Ado and nitrite, and show that m6(NO)Ado induces neoplasms in the reproductive system of mice, an unusual target for a N-nitroso carcinogen.

Adenocarcinoma↗
PubMed1979

N6(Methylnitroso)adenosine: a carcinogenic nitrosamine derived from a naturally-occurring nucleoside.

N6(Methylnitroso) adenosine (M6(NO)Ado) is found readily under acidic conditions by the interaction of nitrite with 6-methyladenosine, a naturally-occurring nucleoside. Swiss mice were treated with M6(NO)Ado by injection (40 mg/kg each treatment) transplacentally and then as newborns and young adults. The incidences of lymphomas, primary lung tumors, and hepatic neoplasms were significantly greater in these treated animals than in controls. These results demonstrate the tumorigenicity of M6(NO)Ado.

Adenosine↗
PubMed1979

Lung tumorigenesis in mice after chronic exposure in early life to a low dose of dimethylnitrosamine.

Strain A female mice were exposed to 10 ppb dimethylnitrosamine (DMN) in their drinking water for 4 weeks before mating. Treatment was continued through pregnancy and lactation and after weaning until the progeny were 22 weeks old. The incidence of primary lung tumors among the treated progeny (23%) was significantly higher (P less than 0.021) than that among controls (8%). The effect of the DMN was greatest among the males: 32% had lung tumors, compared with 4% of the control males (P less than 0.016). The DMN-exposed females also had a higher lung tumor incidence than did the controls, but the difference was not of statistical significance. These results demonstrate carcinogenicity of DMN at a dose approaching amounts possibly encountered by the human population as a result of environmental exposure.

Adenoma↗
PubMed1978

Two crops of primary lung tumors in BALB/c mice after a single transplacental exposure to urethane.

Transplacental exposure of BALB/c mice to urethane on day 17 of gestation resulted in the appearance of 2 distinct crops of primary lung tumors (adenomas). The first, smaller crop occurred in 6--12% of the offspring by 12 weeks of age. The second crop, seen after 9 months of age, consisted of tumors in 45% of the offspring. This finding indicates a potentially useful model system for studying tumor latency. It also suggests caution in the choice of short endpoints in time carcinogenesis assays based on lung tumors in certain strains of mouse.

Adenoma↗
PubMed1978

3-Hydroxyxanthine: transplacental effects and ontogeny of related sulfate metabolism in rats and mice.

The ontogeny of sulfate metabolism related to the metabolic activation of the carcinogenic purine N-oxide 3-hydroxyxanthine (3-OH-X) was studied in noninbred Sprague-Dawley rats. Sulfotransferase activity toward 3-OH-X was detectable in most fetal livers near term at about 25% of adult values and increased slowly after birth. This activity was also present in placentas. Compared to 3-OH-X sulfotransferase, sulfotransferase activity toward p-nitrophenol was lower in fetal livers and was not detected in placentas. Sulfohydrolase activity toward 3'-phosphoadenosine-5'-phosphosulfate was higher in fetal and newborn livers and in placentas than in adult liver. In a parallel transplacential carcinogenicity assay, a low but significant percentage of male rats exposed as fetuses to multiple high doses of 3-OH-X developed single liver carcinomas. After the lowest transplacental dose, the incidence of degenerative kidney disease in old male offspring was significantly higher than that in controls. In an assay with mice, (C57BL/6 X BALB/c)F1 mice exposed transplacentally to 3-OH-X experienced significantly greater perinatal morality and fewer lung adenomas among the surviviors at 20 months of age than did the controls.

Animals↗
PubMed1978

Increased incidence of mammary tumors in rats after direct or transplacental exposure to 3-hydroxyxanthine.

Rats were exposed directly or transplacentally to the carcinogenic purine N-oxide 3-hydroxyxanthine (3-OH-X). Among female noninbred Wistar rats given 3-OH-X sc, beginning at suckling or weaning ages, there was a significantly greater proportion of mammary tumor bearers and a higher mean number of mammary tumors per rat than among controls. This effect was seen even at low doses producing no other neoplasms such as hepatic carcinomas or fibrosarcomas and fibromas at the site of injection. Noninbred Sprague-Dawley rats, treated transplacentally with 3-OH-X by ip injection into pregnant females, also also had a significantly greater incidence of mammary tumors than did controls.

Age Factors↗
PubMed1978

Transplacental lung tumorigenesis in the athymic mouse.

Female BALB/c nu/+ mice, pregnant by nu/+ males (nu: gene for hairlessness-athymia) were given injections of urethan, a transplacental tumorigen, on Day 17 or 19 of gestation. After an average of 16 weeks under clean conventional conditions, the incidence of primary lung tumors was similar in nude and normal offspring treated with carcinogen on either gestational day, with a higher incidence after treatment of Day 19. Thus, the absence of thymus did not affect the occurrence of transplacentally induced primary lung tumors or alter the well-known perinatal increase in sensitivity. Histologically, the nu/nu tumors differed from normal in the appearance of many atypical basophilic cells and in a tendency to invade both the parenchyma and the pleural surface. These results suggested progression of the lung adenomas to a more atypical, invasive form, a progression that may have occurred prematurely in the absence of thymus-dependent immune response.

Adenoma↗
PubMed1978

Effects of imipramine, nitrite, and dimethylnitrosamine on reproduction in mice.

Administration of the tricyclic dibenzazepine drug imipramine, a tertiary amine, in the food (100 mg/kg) or sodium nitrite (1 g/liter) or dimethylnitrosamine (0.1 ppm) in the drinking water of Swiss CD-1 mice before and during pregnancy, resulted in increased perinatal death of the offspring compared to controls. Administration of imipramine and nitrite together had no effect on perinatal survival, but instead resulted in infertility or delayed impregnation in some females. A biological synergism or in vivo chemical interaction of the two chemicals is suggested.

Animals↗
PubMed1975

Considerations of delta 5-pregnenediol formation in ovarian tissue.

20Alpha-Hydroxypregn-4-ene-3-one (20alpha-DHP) in ovarian tissue could be formed directly from progesterone (Pathway 1) or from pregnenolone via a delta 5-intermediate, pregn-5-ene-3beta, 20alpha-diol (Pathway 2). The participation of Pathway 2 is demonstrated to the extent that pregnenediol can be formed from pregnenolone and that the delta 5-diol, in turn, can be a precursor to 20alpha-DH P in vitro, using ovarian tissue from cycling rats by both flask incubation and superfusion techniques. Pathway 2 would allow greater flexibility and local regulation with respect to potential steroid sulfate conjugates of delta 5-3beta-OH intermediates. The existence of two pathways leading to 20alpha-DH P could explain the occurrance of variable levels of this steroid without a necessary direct or inverse relationship to progesterone secretion levels at different stages of the estrous cycle.

Animals↗
PubMed1971

The dependence of cecropia yolk formation in vitro on specific blood proteins.

The capacity of cecropia vitellogenic follicles to form yolk during short-term in vitro incubation in female blood was analyzed by labeling with fluorescein-conjugated serum globulin, tritiated cecropia blood proteins, or tritiated amino acid. As judged by fluorescence microscopy or autoradiography, yolk formation during 3-8 hr in vitro was similar in rate and in protein uptake specificity to that observed in vivo. When follicles were incubated in cecropia male blood, 6% gamma globulin, or cecropia saline, the yolk produced was markedly inferior in quality and quantity to that generated in female blood. Purified preparations of vitellogenin, the primary female blood protein deposited in the yolk, were equivalent to whole female blood in supporting yolk formation; this protein seems, therefore, to have a specific stimulatory role. An enhancement of the rate of pinocytosis at the oocyte surface by vitellogenin is postulated.

Amino Acids↗
PubMedDate not supplied

Alcohol-related cancer risk: a toxicokinetic hypothesis.

Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further.

Animals↗