Induction of DNA adducts and mutations in spleen, liver and lung of XPA- deficient/lacZ transgenic mice after oral treatment with benzo[a]pyrene: correlation with tumour development

We were interested to study the relationship between DNA lesions, DNA repair, mutation fixation, and tumour development. Therefore, mice harbouring lacZ reporter genes and being either wild-type or defective in the DNA excision repair gene XPA, were treated with the genotoxic carcinogen benzo[a]pyrene at an oral dose of 13 mg/kg b.w. (3 times/week). At different time points, i.e. 1, 5, 9 or 13 weeks after start of the oral administration, levels of BPDE-N2-dG adducts (the major formed DNA adduct by benzo[a]pyrene in mice), and lacZ mutation frequencies were measured both in target (spleen) and non-target (lung and liver) tissues. Both in wild-type and XPA-deficient mice, benzo[a]pyrene treatment resulted in increased BPDE-N2-dG adduct levels in all three tissues analysed. In XPA-deficient mice, BPDE-N2-dG adduct levels still increased up to 13 weeks of oral benzo[a]pyrene treatment, whereas in DNA repair proficient mice steady-state levels were reached after 5 weeks of treatment. After 13 weeks, the BPDE-N2-dG adduct levels observed in XPA-/- mice, were 2- to 3-fold higher than the steady state levels observed in XPA+/+ mice in the same tissues. Mutation frequencies in the lacZ reporter gene were the same in wild- type and XPA-deficient mice that were treated with the solvent only. Oral benzo[a]pyrene treatment resulted in an increase in mutation frequency in the lacZ marker gene in all three tissues, but this increase was most profound in the spleen. After 13 weeks of treatment, a 7-fold increase in lacZ mutation frequency was detected in the spleen of wild-type mice as compared to mutation frequencies in control mice. At the same time point, a 15-fold increase in lacZ mutation frequency was observed in the spleen of XPA-deficient mice. The data presented here show, that a defect in NER mainly results in enhanced mutation frequencies in lymphocytic cells after oral treatment with the genotoxic compound benzo[a]pyrene. Interestingly, as we established in a previously performed carcinogenicity assay, the same oral treatment with benzo[a]pyrene induced lymphomas residing in the spleen of XPA- deficient mice.      

The wandering spleen

Marfan's syndrome has diverse manifestations that overlap with those seen in other connective tissue disorders. Visceral diverticula have been described only once in four adults with marfanoid features of recessive inheritance. Two siblings of a consanguineous marriage with marfanoid features, visceral diverticula, and diaphragmatic eventration are reported.     

Retrograde ileography: value of glucagon

Many gastrointestinal diseases have a predilection for the terminal ileum. Retrograde ileography is a valuable technique for evaluating this region. However, this procedure necessitates reflux of barium (with or without air) into the terminal ileum. This does not often spontaneously occur during a barium enema study. The use of glucagon in double-contrast studies of the colon has been recommended for various reasons, one of which is to facilitate reflux of barium into the terminal ileum. This randomized, double-blind trial confirms that glucagon does promote reflux. Multiple regression analysis indicates that the independent variables of patient age, weight, and sex have little effect on the frequency of reflux. It is concluded that glucagon can facilitate examination of the distal small bowel during a double-contrast colon examination.     

Nonpalpable breast lesions: diagnosis with slightly overpenetrated screen-film mammography and hook wire-directed biopsy in 1,014 cases

Slightly overpenetrated screen-film mammography and hook wire-directed localization were used in 1,014 breast biopsies performed for nonpalpable, mammographically detected breast abnormalities. One lymphoma and 205 breast cancers (20%) were found; 115 breast cancers (56%) were noninvasive, and 90 (44%) were invasive. Mastectomy was performed in 69 breast cancers (34%); 136 (66%) were treated conservatively, 28 with biopsy only and 108 with lumpectomy, node dissection, and radiation therapy. All patients with noninvasive breast cancers treated with axillary dissection had uninvolved lymph nodes. Of the 90 invasive breast cancers, six (7%) had metastases to axillary nodes, which, to the authors' knowledge, is lower than percentages reported in other studies of wire-directed breast biopsies. The authors believe that the slightly overpenetrated technique is a valuable adjunct to screen-film mammography.