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F Canzian

Publications and source records attributed to F Canzian.

34 records · Page 2Linked to original sources
PubMed1996

Microsatellite instability and loss of heterozygosity on chromosome 10 in rat mammary tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Microsatellite instability (MI) and loss of heterozygosity (LOH) were examined in mammary tumors induced in Sprague-Dawley x F344 F1 female rats by 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Examination of 62 microsatellite loci revealed MI in nine of 15 (60%) PhIP-induced mammary tumors, and five of these MI-positive tumors had mutations in more than one microsatellite locus. In contrast, two of 12 (17%) 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were MI positive but had mutations at only one locus each. Further, by using 37 polymorphic markers specific LOH was observed in four of 15 PhIP induced mammary tumors on distal parts of rat chromosome 10, which is homologous to human chromosome 17q with no background level of LOH. Similarly, DMBA-induced mammary tumors showed specific LOH on the same region of chromosome 10. These data suggest that mismatch-repair deficiency and loss of chromosome 10 are involved in carcinogenesis of PhIP-induced rat mammary tumors.

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PubMed1996

A polygenic model of inherited predisposition to cancer.

Polygenic inheritance of predisposition to cancer is demonstrated in experimental animals for different tumor types. Genetic susceptibility to hepatocarcinogenesis, lung tumorigenesis, skin and intestine carcinogenesis, and plasmacytomagenesis is determined by inheritance of multiple cancer predisposition and resistance alleles, whose chromosomal locations have been found by genetic linkage analysis. In some of these experimental models, genetic heterogeneity has also been reported. In humans, increased risk of lung cancer associated with multiple genes coding for drug metabolizing enzymes, increased risk of cancer in relatives of cancer patients, and genetic heterogeneity are compatible with polygenic inheritance of cancer predisposition. Polygenic inheritance based on the combination of multiple alleles that give predisposition and resistance to cancer would predict a very high risk of cancer in carrier individuals and a marginal increase in the relative risk of cancer in the progeny of the cancer patients. Therefore, predisposition to cancer may be genetically determined even in the absence of familial clustering of cases.

Animals↗
PubMed1996

Identification of 29 rat genetic markers by arbitrarily primed polymerase chain reaction.

The number of genetic markers for the rat is still limited, in spite of its wide use in cancer research. To facilitate accurate mapping of both established and novel rat genetic markers, we constructed a linkage map by genotyping 105 F2 rats from ACI/N (ACI) and BUF/Nac (BUF) crosses. This map consists of 120 genetic markers that had been previously reported, mainly by two research groups, but had not been integrated. To find new genetic markers, the arbitrarily primed polymerase chain reaction (AP-PCR) was applied to detect polymorphic bands between ACI and BUF rats. After testing 56 single primers and 12 combinations of primers, we found 36 bands produced by 16 single primers and two combinations to be reliably polymorphic between ACI and BUF rats. The 36 bands were typed in the 105 F2 rats, and 29 of them could be linkage-mapped. AP-PCR is thus useful to detect new genetic markers in laboratory strains of rats.

Animals↗
PubMed1995

Construction of a phylogenetic tree for inbred strains of rat by arbitrarily primed polymerase chain reaction (AP-PCR).

We constructed a tentative genealogic tree of 13 inbred rat strains using genetic markers identified by the AP-PCR (Arbitrarily Primed Polymerase Chain Reaction) technique, which consists of PCR amplification under low stringency conditions, with only one oligonucleotide as both forward and reverse primers. We obtained discrete-state genotypes of 264 loci, presumably covering the whole rat genome. Computational analysis of this panel allowed the construction of a genealogic tree representing the relations among the 13 strains. The accordance of the present results with available data on the histories of some of these strains validates the use of the AP-PCR technique for studies on phylogeny.

Animals↗
PubMed1995

Mapping of body weight loci on mouse chromosome X.

Inheritance of overweight in humans appears to be under polygenic control. Study on the mouse model may help to determine candidate regions in human genome for the search of overweight genes. Inbred mouse strains showed wide variation in body weight and can provide an experimental model for the study of inheritance of overweight. By genetic linkage analysis, we report the mapping of two loci, named Bw1 and Bw2 (body weight 1 and 2), on Chromosome (Chr) X that strongly affect adult body weight in two interspecific testcross male populations (HSB) and ASB) of mice. In addition, another locus, named Bw3, is also mapped on Chr X in ASB populations. These loci account for up to 24% of the phenotypic variation in both populations. Considering the conserved synteny between mouse and humans Chr X, these results provide candidate regions on Chr X that can be tested for linkage with overweight in humans.

Animals↗
PubMed1995

Genetic polymorphisms and susceptibility to cancer development.

Humans show heterogeneous susceptibility to cancer development, suggesting the involvement of various genetic backgrounds in control of the production of endogenous carcinogens, the metabolism of carcinogens, the repair of DNA damage, cell proliferation and defence mechanisms including immune reactions. Gastric cancer is the major cancer in Japan. However, little is known about the genes linked with its development. In 1967, we found that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric cancers in Wistar rats. Subsequently the Buffalo strain of rats was reported to be resistant to MNNG stomach carcinogenesis, while ACI rats were very sensitive. In a carcinogenesis study using F1 and F2 rats, we suggested that this trait of MNNG stomach carcinogenesis-resistance was regulated by a single autosomal dominant allele. The O6-methylguanine adduct levels in gastric mucosa induced by MNNG were the same in Buffalo and ACI rats, but cell proliferation induced by MNNG was much higher in ACI than Buffalo animals. Chromosome mapping of the gene responsible for susceptibility to MNNG-induced carcinogenesis is now in progress and its identification will hopefully give us clues to the involvement of genetic traits in susceptibility to gastric cancer in humans. In addition, the genetic background of susceptibility to breast cancer is also being studied. In Japan, about 5% of all cases of breast cancer are familial. We have studied BRCA1, the breast cancer susceptibility gene, as a determinant of susceptibility to breast cancer by linkage analyses in 11 families, but our results indicate that BRCA1 may not be important for development of familial breast cancer in Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1994

Instability of microsatellites in rat colon tumors induced by heterocyclic amines.

Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/mircrosatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6- phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f] quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis.

Animals↗
PubMed1994

Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice.

The C3H/He mouse represents a good experimental model of genetic predisposition to hepatocellular tumor development. We analyzed an interspecific test-cross population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice, typed with 222 genetic markers to locate precisely the hepatocellular tumor susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a significant linkage with hepatocellular tumor development, as indicated by different quantitative indexes estimating liver tumor size. Liver tumor frequency was not genetically controlled. These loci are different from three other Hcs loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed with the resistant laboratory strain A/J. The present result indicates a multigenic model of inheritance for hepatocellular tumor susceptibility.

Animals↗
PubMed1994

Comparative mapping of the actin-binding protein 280 genes in human and mouse.

Two genes encode actin-binding protein 280 isoforms. ABP-280 or filamin (FLN1) is present in the cytoskeleton of many cell types, whereas expression of FLN2 is limited to skeletal muscle and heart. FLN1 maps to human chromosome Xq28, and, by physical mapping in YAC clones, we have mapped the homologous murine locus (Fln1) to mouse chromosome X, in a region of syntenic homology with human chromosome X. We mapped FLN2 to human chromosome 7q32-q35 by analysis of somatic cell hybrids containing portions of chromosome 7, and, by using a mapping panel from an interspecific murine cross, we mapped the corresponding murine locus (Fln2) to murine chromosome 6 in a region homologous to human chromosome 7.

Animals↗
PubMed1994

Expression in lung tumors and genetic mapping of the novel murine protein kinase C eta.

Protein kinase C eta (nPKC eta) is a member of the protein kinase C family with a unique tissue distribution in skin and lung. We analyzed nPKC eta expression in normal murine lung and in 36 lung tumors induced by urethane in AC3 F1 and F2 mice. The nPKC eta-related transcript was present at fivefold to tenfold lower levels in tumors than in normal lung controls. We mapped two distinct loci for nPKC eta on murine chromosome 12, using linkage analysis in an interspecific test cross. The results indicate that the mouse Pkcn-rs1 and Pkcn-rs2 loci were about 30 cM from the centromere and about 2 cM from each other.

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PubMed1993

Chromosome mapping of murine susceptibility loci to liver carcinogenesis.

The validity of mouse liver tumors is controversial in the risk assessment of carcinogenicity of chemicals in humans, because mice used in carcinogenicity bioassays are genetically predisposed to liver tumors. The argument could be resolved once liver tumor susceptibility genes have been cloned and their role in liver tumor development elucidated. We performed a genetic linkage analysis to map murine liver tumor susceptibility genes, as a first step toward their identification. An F2 population of 87 urethane-treated male A/J x C3H/He mice was scored with 83 genetic markers. Three regions, localized on chromosomes 7, 8, and 12, were found to contain putative liver tumor susceptibility genes.

Animals↗
PubMed1993

A major susceptibility locus to murine lung carcinogenesis maps on chromosome 6.

Lung tumours represent a major cause of death in humans, and although smoking represents the main pathogenetic factor, inheritance also plays a part. However, the identification of possible predisposing genetic factors is difficult, because of their low penetrance. We took advantage of murine strains that are genetically susceptible or resistant to lung tumour development, to map murine genes associated with susceptibility to lung carcinogenesis. An F2 population of urethan-treated A/J x C3H/He mice was scored with 83 genetic markers. A chromosome 6 distal region, spanning mice was scored with 83 genetic markers. A chromosome 6 distal region, spanning 35 centiMorgans, contained a major lung tumour susceptibility locus. No other chromosomal region was significantly associated with lung tumour development.

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PubMedDate not supplied

Hepatocarcinogenesis: a polygenic model of inherited predisposition to cancer.

The murine inbred strain C3H provides an experimental model of inherited predisposition to hepatocellular cancer. Hepatocellular neoplastic lesions induced by chemical carcinogens reach a volume 10-100-fold greater in C3H mice than in genetically resistant strains. However, the huge strain differences in tumor size are explained by relatively small differences (10%-30%) in tumor cell kinetics. Genetic linkage experiments in different crosses demonstrated that six unlinked hepatocarcinogen sensitivity (Hcs) and two hepatocarcinogen resistance (Hcr) loci determined quantitative variations in susceptibility to hepatocarcinogenesis. Such results provide the genetic basis for the strain variations in susceptibility to hepatocarcinogenesis and demonstrate a new model of polygenic inheritance of predisposition to cancer.

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