Histocompatibility genes (theH-2 complex) and susceptibility to spontaneous lung tumors in mice

Faraldo, Maria José; Dux, Anna; Mühlbock, O; Hart, Guus

doi:10.1007/bf01570433

“…Whereas the congeneic strains AlSn (H-2") and A.SW (H-29 were highly susceptible to DMN, comparison of BlO.A, B1O.AKM and B10 revealed that the introduction of H-2" and H-2" on a B10 background results in significantly increased lung tumour incidences as compared to the B10 strain itself. These results on induced lung tumours are in good agreement with those on spontaneous lung tumour formation (Faraldo et al, 1979). Also, our finding that B1O.AKM is more susceptible than B10 is in accordance with the result obtained by Faraldo et al (1979), whereas it contradicts that of Smith and Walford (1978).…”

Section: Discussionsupporting

confidence: 94%

“…These results on induced lung tumours are in good agreement with those on spontaneous lung tumour formation (Faraldo et al, 1979). Also, our finding that B1O.AKM is more susceptible than B10 is in accordance with the result obtained by Faraldo et al (1979), whereas it contradicts that of Smith and Walford (1978). These authors found no difference in spontaneous lung tumour susceptibility between strains B1O.AKM and B10.…”

Section: Discussionsupporting

confidence: 94%

“…This study confirms and extends earlier observations (Faraldo et al, 1979;Smith and Walford, 1978) on the relationship between the H-2 histocompatibility system and lung tumour development. In our experiments the susceptibility to lung tumour formation in H-2 congeneic strains was studied in mice treated with a chemical carcinogen (DMN).…”

Section: Discussionsupporting

confidence: 93%

“…In the experiments on spontaneous lung tumour formation (Faraldo et al, 1979), most of the tumours can-on the basis of the descriptions and Figures given-be interpreted as papillary ones. In our study, lung tumour incidences in untreated animals were too low to permit a definite conclusion with regard to tumour type.…”

Section: Discussionmentioning

confidence: 99%

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Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine‐induced tumour formation in relation to H‐2 haplotype

Engelse

¹

,

Oomen

²

,

Valk

³

et al. 1981

Intl Journal of Cancer

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Male mice of the strain A/Sn, of its congeneic partner strain A.SW, C57BL/10ScSnA (abbreviated: B10), and of two congeneic strains on a B10 background (B10.A and B10.AKM) were investigated for their susceptibility to lung tumour induction by dimethylnitrosamine (DMN) administered either by intraperitoneal injection or in the drinking water. Strain B10 (haplotype H-2b) proved to be very resistant, whereas strains A/Sn (H-2a) and A.SW (H-2s) were highly susceptible. The introduction of the haplotypes H-2a and H-2m in the resistant strain B10 resulted in a significant increase in sensitivity towards DMN-induced lung tumour formation. Lung tumour incidences in male (B10.A x B10)F hybrids, receiving DMN in drinking water, were found to be intermediate between, and significantly different from, the incidences of identically-treated parent strains B10.A and B10. Males of back-cross (B10.A x B10) x B10 BC proved to be of low susceptibility to lung tumour formation by DMN, tumour incidence being very low and not significantly different from that observed in identically-treated B10 males. It is concluded that, at least in the model system of B10-derived congeneic strains, H-2 haplotype is one of the factors important in determining susceptibility towards DMN-induced lung tumours. Comparison of C3Hf (H-2k), C3H/Sn (H-2k) and the latter's congeneic strains C3H.B10 (H-2b) and C3H.NB (H-2p) of male mice showed that these strains were moderately susceptible to both lung tumour and hepatoma formation by DMN. Accordingly, the presence of an H-2 haplotype from a lung-tumour-resistant strain (H-2b, B10) on the background of a strain of intermediate susceptibility (C3H) does not decrease susceptibility to lung tumour formation. The results were considered in the light of the H-2 haplotype dependence of spontaneous lung tumours, and consequently attention has been paid to the histological types of the induced and spontaneous lung tumours.

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“…The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively ( p = 0.03). In experimental models, the major histocompatibility complex (MHC) has an interactive influence on the development of spontaneous, virally or chemically-induced malignancies (Lilly et al, 1964; Boyse et al, 1972;Faraldo et al, 1979;Oomen et al, 1988;Vasmel et al, 1988). Particular alleles of this polymorphic system influence the incidence and phenotype, as well as the age at onset of malignancies (Vasmel et al, 1988;Miyazawa et al, 1992).…”

mentioning

confidence: 99%

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Dorak

¹

,

Machulla

²

,

Hentschel

³

et al. 1996

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The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and I I 6 of controls were also typed by HU-DR6 PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively ( p = 0.03). In experimental models, the major histocompatibility complex (MHC) has an interactive influence on the development of spontaneous, virally or chemically-induced malignancies (Lilly et al., 1964; Boyse et al., 1972;Faraldo et al., 1979;Oomen et al., 1988;Vasmel et al., 1988). Particular alleles of this polymorphic system influence the incidence and phenotype, as well as the age at onset of malignancies (Vasmel et al., 1988;Miyazawa et al., 1992). The interaction of the MHC is not exerted on transformation of a neoplastic clone but occurs during the pre-leukaemic stage (Chesebro, 1981;Lonai et al., 1982). Thus, it does not contain essential susceptibility genes but influences the rate of progression to overt malignancy. More than one MHC gene is involved in the complex, multifactorial development of malignancies (Oomen et al., 1988;Zijlstra and Melief, 1986). Eight of theThe findings in animal models stimulated similar studies investigating the role of the human MHC (HLA complex) in malignancies. The initial serological studies uncovered some associations but did not establish a strong and consistent influence of HLA antigens on the development of neoplasms (Tiwari and Terasaki, 1985). The haemopoietic malignancies have been the most extensively studied ones (Seremetis et al., 1985;Bortin et al., 1987;Caruso et al., 1987;Richter et al., 1973;Nunez-Roldan et al., 1982; Kilpatrick et al., 1984;Dyer et al., 1986;Cuttner et al., 1994). In leukaemia and lymphoma also, no consistent HLA association has been shown by serology.With the advent of molecular typing methods, this issue has been revisited. Recent studies have shown stronger allelic associations, although genotypes, age and gender effect have usually been overlooked (Apple et al., 1994;Klitz et al., 1994). The first DNA-based study investigating the role of the HLA complex in the development of leukaemia showed a strong influence of several independent genotypes on the age at onset of chronic myeloid leukaemia (CML), the strongest one being homozygosity for the supertypic specificity HLA-DR53 (Dorak et al., 1994a). A second molecular study confirmed the role of this homozygous genotype in increased susceptibility to childhood acute lymphoblastic leukaemia (ALL) and also showed a gender effect (Dorak et al., 1995).In the present study, the same association and its influence on the age at onset of chronic lymphoid leukaemia (CLL) were investigated by DNA analy...

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Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Dorak

¹

,

Machulla

²

,

Hentschel

³

et al. 1996

Intl Journal of Cancer

View full text Add to dashboard Cite

The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and 116 of controls were also typed by HLA-DRB PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively (p = 0.03). Eight of the 9 homozygous patients were under the median age. The sex ratio in the DR53 homozygous group was reversed in favour of females. The homozygosity rates for DR53 were different in the overall groups of patients and controls, yielding a relative risk (RR) of 2.4 (p = 0.03). This association was stronger in the early-onset group compared to age-matched controls (RR = 4.4; p = 0.008) and for females with an early onset compared to age- and sex-matched controls (RR = 17.9; p = 0.0008). The simultaneous occurrence of the alleles of the haplotype A2B62DR4 showed a strong association with CLL (RR = 4.1; p = 0.002). This was probably the reason behind the association with HLA-DRB1*0401 (RR = 2.4; p = 0.009). Compared to the accelerating effect of HLA-DR53, HLA-DR52 showed a significant delaying effect on the onset of CLL. These findings confirmed the influence of the HLA complex on the development of another leukaemia.

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Histocompatibility genes (theH-2 complex) and susceptibility to spontaneous lung tumors in mice

Cited by 24 publications

References 6 publications

Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine‐induced tumour formation in relation to H‐2 haplotype

Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine‐induced tumour formation in relation to H‐2 haplotype

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

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