Flow cytometric DNA and cytogenetic studies in human tumors: a comparison and discussion of the differences in modal values obtained by the two methods.

The numerical chromosome values in 53 human tumors were determined and compared with the modal DNA values as measured by flow cytometry. In tumors with chromosome counts in the diploid and tetraploid range, the modal DNA values were found to correspond to the modal values based on the chromosome counts. In tumors with chromosome counts in the triploid range, however, the modal DNA values were about 15% higher than expected. In order to explain this difference, the ratio between large and small chromosomes in the karyotyped metaphases was assessed. In addition, the DNA content of individual chromosomes, including markers and minutes, was calculated as a reflection of the DNA content of the whole cell. The ratio of large to small chromosomes did not deviate from the normal ratio found in cells with diploid, triploid, and tetraploid chromosome counts. Neither difficulties in karyotyping nor short-comings in the flow cytometric methodology could be used to explain the discrepancy between the expected and empirical modal DNA values. Some of the chromosomes in triploid tumors may, therefore, contain an increased amount of DNA.

Chromosomal and DNA patterns in transitional cell bladder carcinoma. A comparative cytogenetic and flow-cytofluorometric DNA study.

Biopsy tissue from 71 bladder tumors in 57 patients was studied by chromosome analysis and flow cytofluorometry. Chromosome analysis was hampered by preparation difficulties and was successful in only 53% of the analyzed tumors. DNA analysis failed to reveal near-diploid deviations, while the grossly aneuploid tumors generally had DNA values 10% to 15% above the numerical chromosome counts. Noninvasive tumors were diploid-near-diploid with occasional markers. Superficially invasive tumors were both diploid-near-diploid and near-tetraploid, but with a chromosome count of only 80 in the latter cases. Deeply invasive tumors tended to be triploid on DNA analysis, and had chromosome counts in the vicinity of 60. In addition to single chromosome abnormalities, increased malignancy apparently is also associated with an increased total number of chromosomes. A tetraploid DNA level seems to represent a more stable genome, although chromosomes show gross abnormalities including markers.

Cytogenetic analysis of 62 transitional cell bladder carcinomas.

Chromosome analysis of biopsy material obtained after vinblastine pretreatment was carried out in 108 specimens from 89 patients with transitional cell carcinoma of the urinary bladder. Analyzable metaphases were obtained in 62 tumors, but only in nine tumors could karyotypes be analyzed by banding; a conventional technique was used in all others. Ploidy and occurrence of markers corresponded with tumor morphology and invasion and sometimes aided in the clinical evaluation; chromosome anomalies specific for bladder cancer were not revealed. In noninvasive tumors of WHO grade 1 and 2, near-diploid karyotypes with occasional marker chromosomes dominated. Grade 3 tumors showed a variety of grossly aneuploid karyotypes, with an almost constant occurrence of different markers. Superficially invasive G2 tumors had moderately pronounced aberrations with more deviations than non-invasive tumors but without the great variety of G3 tumors.

Chromosome analysis and sister chromatid exchange in encephalo-trigeminal angiodysplasia.

A female, aged 32, with facial birthmarks and suffering migraine headaches and a slight hemiparesis was examined with isotope scanning, CT and angiography. She was found to have a massive, unilateral angiodysplasia, transforming the right cerebral hemisphere into an expanding vascular sponge-like structure. There was a family history of red facial birthmarks. The patient and her father were analysed cytogenetically by estimating the frequency of chromosome aberrations and sister chromatid exchanges (SCE). The frequency of gaps and breaks was normal compared to healthy controls, but the patient showed a significantly higher level of spontaneous SCE's. The patient and her father also had a higher than normal number of SCE's after addition of mitomycin C (MMC) to the blood culture. Numerical and structural chromosome deviations markedly exceeded normal in both, possibly representing a genetic imbalance in this syndrome.

Chromosome and DNA cytometric study of a papillary carcinoma of the bladder with a high stemline and numerous double minutes.

A papillary cancer of the bladder [WHO grade 3] was studied with chromosome and DNA analysis. A high frequency of mitoses was noted, and analysis of 151 metaphases revealed a dominating stemline in the pentaploid region. More than 95% of the cells contained double minutes (dm). Flow cytometry showed the dominant stemline to be in the hexaploid region, that is, about 20% above the numerical chromosome value. This difference is generally obtained when these two methods are compared and is not influenced by the presence of dm. Both methods have been complementary in the evaluation of this tumor.

Investigation of the mechanism of perforation of an intrauterine device in pigs and dogs.

In the last few years the risk of perforations in connection with the insertion and later use of intrauterine devices (IUDs) has been the subject of much discussion in Sweden. In this experimental study, which was carried out on five pigs and nine dogs and in which four different types of IUDs were used, the following clinical situations encountered in women were simulated: IUD in correct position in the uterus, IUD in an adverse position in the uterus, and IUD more or less inserted through the uterine wall. The animals were observed for 3 to 6 months. The findings indicate that, when perforation occurs, it is most probably ascribable to the insertion procedure.

The possible risks of a copper and an inert intrauterine device situated in the abdominal cavity: an experimental study in pigs and dogs.

The possible injurious effects of abdominal intrauterine devices (IUDs), including Cu-IUDs, inert IUDs, and "closed' IUDs, were evaluated in an experimental study. Pigs and dogs were used as they have, respectively, a propensity to form adhesions and a pronounced tendency to develop serious peritonitis. The reactions expected in humans might be intermediate to those found in these two kinds of experimental animals. The results of this study indicate that an inert or copper-bearing IUD usually remains in its initial position in the abdominal cavity, encapsulated by adhesions. The risk of strangulation of the intestine by a "closed' IUD seems minimal.

Sister-chromatid exchanges and chromosomal aberrations in rats treated with phenacetin, phenazone and caffeine.

To study chromosomal aberrations and the frequency of sister-chromatid exchanges (SCE) a long-term chronic toxicity study was performed in rats treated with phenacetin, phenazone and caffeine, alone and in different combinations. Compared with controls, aberrations such as gaps, breaks and structural dearrangements were only increased in the group treated by phenacetin alone. After mitomycin C treatment of the blood culture, the aberrations were markedly, but not significantly, increased. All experimental groups showed a higher SCE frequency, most deviating in the rats treated with phenacetin alone. This correlates with the fact that phenacetin is a strong general carcinogen.

Colonoscopic biopsies and cytological examination in chronic ulcerative colitis.

Both multiple colonoscopic biopsies and brushing specimens for detection of any premalignant epithelial lesion were taken in 50 patients with long-standing ulcerative colitis. In 25 of the cases centrifuge sediment of enema return before the endoscopy was examined cytologically. The three methods were compared with respect to yield of colonic epithelium and occurrence of epithelial atypia. Enema return contained only a little glandular epithelium, which showed no atypical changes. Both biopsy and brushing yielded an abundance of epithelium. Biopsies showed a considerably higher frequency of epithelial atypia, especially of mild degree, and in two cases precancerous lesions were demonstrated only in the biopsies. In seven cases, on the other hand, moderate or severe atypia was found in brushing specimens when biopsies only revealed mild reactive changes.

Chromosome analysis in meningeal carcinomatosis.

A 50-year-old man with clinical signs of meningeal carcinomatosis is described in whom cerebrospinal fluid cells suspected of malignancy were found. A chromosome analysis confirmed malignancy and also indicated the origin of the primary tumor.