Studies on lung tumours. IV. correlation between [3H]thymidine labelling of lung and liver cells and tumour formation in GRS/A and C3Hf/A male mice following administration of dimethylnitrosamine

Munter, Hans; Engelse, L. Den; Emmelot, P.

doi:10.1016/0009-2797(79)90079-6

Cited by 25 publications

(2 citation statements)

References 15 publications

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“…Alternatively, hepatocellular modifier loci may act directly through alteration of the E2F1 pathway, with such alteration, already apparent in the normal liver, underlying the high growth rate of hepatocellular tumors in the susceptible mice 25. Consistent with the hypothesis of an early dysregulation of cell‐cycle control, already apparent in the normal liver and associated with genetic susceptibility to hepatocarcinogenesis, higher thymidine labeling indices have been reported in the normal parenchymal liver cells of C3H than of strains genetically resistant to hepatocarcinogenesis 26, 27…”

Section: Discussionmentioning

confidence: 76%

Genetic control of resistance to hepatocarcinogenesis by the mouseHpcr3locus

et al. 2008

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The genome of the BALB/c mouse strain provides alleles that dominantly inhibit hepatocellular tumor development in F1 crosses with the highly hepatocarcinogenesis-susceptible C3H/He strain. Genome-wide linkage analysis using a 1536 -single-nucleotide polymorphism array in a (C3H/He ؋ BALB/c)F2 intercross population treated with urethane to induce hepatocellular tumor development revealed a locus with a major role in the resistance to hepatocarcinogenesis. This locus, designated hepatocarcinogen resistance 3 (Hpcr3) and mapping to central chromosome 15, showed a linkage at LOD score ‫؍‬ I nbred strains of laboratory mice constitute disease models that have allowed characterization of the genetic determinants of inherited susceptibility to different types of tumorigenesis, because they display a wide range of spontaneous and chemically induced tumor incidence. 1 In particular, the mouse hepatocellular tumor model provided the first formal demonstration of the polygenic nature of inherited cancer predisposition. 2 C3H/He mice represent one of the strains most susceptible to hepatocarcinogenesis. In this strain, genetic susceptibility to hepatocarcinogenesis is associated with the size but not with the number of liver neoplastic lesions, suggesting that tumor growth/progression but not tumor initiation is genetically controlled. 3 Crosses between C3H/He mice and the resistant C57BL/6J or A/J strain produce F1 hybrids in which the susceptibility trait is dominant, 4 whereas the same trait is recessive in crosses with the resistant BALB/c strain, which therefore carries dominant tumor resistance alleles. 5 Seven hepatocarcinogenesis susceptibility loci (Hcs1-7) have been mapped in crosses between C3H/He and either C57BL/6J or A/J mice, 2,6 whereas BALB/c-derived alleles have not yet been characterized.We carried out a genetic linkage study to map the BALB/c-derived hepatocarcinogen resistance loci and to identify putative genetic targets of these loci by analysis of the gene expression profile of normal mouse liver. Materials and MethodsMice, Phenotypes, and Tissues. The intercross population consisted of (BALB/cJ ϫ C3H/HeJ)F2 mice (n ϭ 182 males) treated with urethane (300 mg/kg body weight) at 7 days of age, kept without any further treat-

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Section: Discussionmentioning

confidence: 76%

Genetic control of resistance to hepatocarcinogenesis by the mouseHpcr3locus

et al. 2008

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“…Several carcinogenic cytotoxic chemotherapeutic agents could be distinguished from noncarcinogenic agents on this basis (33). GRS/A mice sensitive to lung tumorigenesis but not to liver neoplasia in response to dimethylnitrosamine (DMN) overshot their normal type II cell Lls following DMN administration, but no overshoot occurred in their parenchymal liver cells (34). C3Hf/A mice with the opposite organ susceptibilities to neoplasia also gave the opposite proliferative responses.…”

Section: Genes That Regulate Precursor Cell Turnovermentioning

confidence: 99%

Genetic studies on lung tumor susceptibility and histogenesis in mice.

Malkinson

1991

Environ Health Perspect

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The probability that a mouse develops a pulmonary tumor, as well as the structure of that tumor, are dependent on several genes. Three pulmonary adenoma susceptibility (pas) genes predispose some inbred strains to develop lung tumors, even in the absence of carcinogen exposure, and cause others to be resistant. One pas gene is K-ras, which may also be overexpressed in these tumors in a mutated form capable of transforming cells. Mice with activated Ha-ras transgenes override the resistant pas alleles and are born with lung cancer. Susceptible strains have a higher turnover rate of alveolar type II and bronchiolar Clara cells, those cells from which lung tumors arise, than more resistant strains. A high precursor cell turnover rate correlates with a propensity to neoplasia in other animal models as well, possibly due to low concentrations of endogenous growth regulatory molecules such as corticosterone and protein kinase C (PKC). Neoplastic lung epithelial cells are relatively resistant to glucocorticoids and have low PKC levels. A set of genes other than the pas genes governs the response to tumor modulation by butylated hydroxytoluene (BHT). The genes that determine whether lung tumor multiplicity is enhanced by chronic BHT exposure may regulate the ability to hydroxylate BHT at a tert-butyl position to form BHT-OH, a metabolite with greater tumor-promoting potency than BHT. Inbred and recombinant inbred strain variations in adenoma growth patterns indicate that another set of genes, which we have designated pah for pulmonary adenoma histogenesis, may determine which cell type becomes neoplastic and whether adenomas will undergo malignant conversion.ImagesFIGURE 2.FIGURE 3.FIGURE 3.

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Effect of Genetic Susceptibility on Tumor Induction

Drinkwater¹

1995

Chemical Induction of Cancer

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Studies on lung tumours. IV. correlation between [3H]thymidine labelling of lung and liver cells and tumour formation in GRS/A and C3Hf/A male mice following administration of dimethylnitrosamine

Cited by 25 publications

References 15 publications

Genetic control of resistance to hepatocarcinogenesis by the mouseHpcr3locus

Genetic control of resistance to hepatocarcinogenesis by the mouseHpcr3locus

Genetic studies on lung tumor susceptibility and histogenesis in mice.

Effect of Genetic Susceptibility on Tumor Induction

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