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PubMed2000

Disproportionation and nuclease activity of bis[2-ethyl-2-hydroxybutanoato(2-)]oxochromate(V) in neutral aqueous solutions.

Complex 1, [Cr(V)O(ehba)2]- (ehba = 2-ethyl-2-hydroxybutanoate(2-)) is the most studied model compound of relevance to the biological activity of Cr(V) with regard to Cr-induced cancers. The first detailed kinetic study of disproportionation of 1 under neutral pH conditions (pH 6.0-8.0, [NaClO4] = 1.0 M, 37 degrees C) is reported. Kinetic data were collected by stopped-flow and conventional UV-vis spectroscopies and processed by the global analysis method. The disproportionation, which follows the stoichiometry 3Cr(V) --> 2Cr(VI) + Cr(III) (1), leads to release of 5 mol of H+/3 mol of Cr(V). Reaction 1 is accelerated by phosphate, but is not affected by acetate, HEPES, or Tris buffers. Initial rates of Cr(V) decay are directly proportional to [Cr(V)]0 (0.020-1.0 mM); they increase with an increase in the pH values and decrease in the presence of a large excess of ehba ligand. The first direct evidence for the formation of Cr(IV) intermediates in reaction 1 has been obtained; however, their UV-vis spectral properties were different from those of the well-characterized Cr(IV)-ehba complexes. The Cr(III) products of reaction I in phosphate buffers differ from those in the other buffers. A mechanism is proposed for reaction 1 on the basis of kinetic modeling. Influences of the reaction time and conditions on the extent of plasmid DNA cleavage induced by 1 have been studied under conditions corresponding to those of the kinetic studies. A comparison of the kinetic and DNA cleavage results has shown that direct interaction of 1 with the phosphate backbone of DNA is the most likely first step in the mechanism of DNA cleavage in neutral media. Small additions of Mn(II) ((0.01-0.1)[Cr(V)]0) did not affect the rate and stoichiometry of reaction 1, but suppressed the formation of Cr(IV) intermediates (presumably due to the catalysis of Cr(IV) disproportionation). However, much higher concentrations of Mn(II) ((0.1-1.0)[Cr(V)]0) were required to inhibit DNA cleavage induced by 1. Thus, contrary to previous reports (Sugden, K. D.; Wetterhahn, K. E. J. Am. Chem. Soc. 1996, 118, 10811-10818), inhibition by Mn(II) does not indicate a key role of Cr(IV) in Cr(V)-induced DNA cleavage.

Carcinogens↗
PubMed1999

Chromium(III) interactions with nucleosides and nucleotides: a mass spectrometric study.

Interactions of [Cr(salprn)(H(2)O)(2)]ClO(4) with nucleosides and dinucleotides were studied using electrospray ionization mass spectrometry. The nucleosides 2'-deoxycytidine, thymidine, 2'-deoxyadenosine, 2'-deoxyguanosine, cytidine, adenosine and guanosine form 1 : 1 and 2 : 1 adducts with [Cr(salprn)](+), whereas the dinucleotides CpG, GpC, ApT, TpA and TpC form only the 1 : 1 adducts. Collisional activation (CA) spectra of these adducts reveal that Cr(+) attaches to the bases in nucleosides and to both the phosphate and base, especially cytosine and guanine moieties, in the nucleotides. The sugar residues appear to offer no binding sites as elimination of sugar residues is fairly abundant in the CA spectra of the adducts of many of the nucleosides.

Chromium Compounds↗
PubMed1997

Objective responses after fractionated infusional brachytherapy of unresectable pancreatic adenocarcinomas.

BACKGROUND: The prognosis of unresectable pancreatic adenocarcinoma is poor. Therefore, the treatment potential of an intratumoral infusional brachytherapy using macroaggregated human albumin in combination with radioactive chromic phosphate [32P] was investigated in this group of patients. METHODS: Seventeen patients with unresectable tumors received intratumoral infusional brachytherapy. Treatment and assessment of response was performed with the aid of ultrasonography. RESULTS: Four patients had complete response with a duration ranging from 2-57 weeks and 5 patients had partial response with a duration ranging from 4-21 weeks, corresponding to an objective response of 53% (9 of 17 patients). Six of these patients were alive 33-57 weeks after treatment. Radiation necrosis was observed in 1 patient after a 19,000-gray cumulative radiation dose and a slight decrease in blood counts was observed in 2 patients. CONCLUSIONS: Intratumoral infusional brachytherapy using radioactive colloidal chromic phosphate has the potential to reduce inoperable pancreatic tumors with few side effects.

Adenocarcinoma↗
PubMed1999

An early phase II study of intratumoral P-32 chromic phosphate injection therapy for patients with refractory solid tumors and solitary metastases.

BACKGROUND: In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival. METHODS: Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies. RESULTS: Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found. CONCLUSIONS: Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.

Adenocarcinoma↗
PubMedDate not supplied

Hexavalent chromium-induced congenital abnormalities in chick embryos.

The embryotoxic and teratogenic potential of hexavalent chromium was evaluated in chick embryos. Different concentrations of aqueous solution of potassium dichromate ranging from 1.00 to 100.00 microg per egg were injected into chick eggs before incubation. A dose-dependent embryonic mortality was observed in all the groups examined on days 7 and 14 of incubation. The following malformations were observed in survivors: reduced body size and organs; microphthalmia; micromelia; everted viscera; abnormal and twisted neck, beak and spinal cord; isolated epicarditis; club foot; haemorrhage; and patchy feathers. Total mortality showing embryonic resorption was noted in higher dose groups (25-100 microg per egg) on day 14 of incubation.

Abnormalities, Drug-Induced↗
PubMed1981

Intracavitary chromic phosphate (32P) colloidal suspension therapy.

Two-hundred-eighty-nine patients received treatment with chronic phosphate (32P) colloidal suspension (CPCS) 346 times since 1963. One-hundred-seventy-eight patients received 200 intraperitoneal treatments. One-hundred-fifteen patients received 144 intrapleural treatments. Six patients received both intraperitoneal and intrapleural treatments. Two patients received two intrapericardial treatments. Results of therapy were evaluated three months later and then at yearly intervals. In those patients who survived three months, the referring physician observed improvement in 85% of intraperitoneal treatment and in 75% of intrapleural treatments.

Brachytherapy↗
PubMed1988

Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer.

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.

Carcinoma↗
PubMed1991

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging.

Forty-nine women with apparent Stage I and II ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as the first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.

Chromium↗
PubMed1994

Single-use percutaneous catheters for intraperitoneal P32 therapy.

BACKGROUND: Intraperitoneal (IP) radioactive chromic phosphate (P32) remains investigational in the treatment of patients with ovarian and/or endometrial cancer. Single-use percutaneously placed catheters offer the advantage of therapy without additional surgery. METHODS: Between August, 1986 and October, 1992, 25 patients underwent bedside percutaneous catheter placement under local anesthesia without ultrasonographic or radiologic guidance, using a specialized central venous catheter. RESULTS: Catheter insertion was successful in 22 of 25 patients (88%) with good IP distribution. Of these, 18 of 22 patients (82%) underwent successful catheter placement with one attempt and 4 of 22 (18%) after one to three additional attempts. The technical failure rate was 12%. Multiple catheter placement attempts were associated with an increased incidence of complications (r = 0.63). Bowel entry occurred in 4 of 25 patients (16%) during 5 of 43 attempts at catheter placement (12%) but was without clinical sequelae. The likelihood of bowel entry significantly increased with more than two attempts (P = 0.02). A median of 39 days (range, 7-156 days) elapsed between the preceding laparotomy and catheter insertion. CONCLUSIONS: Percutaneous catheter placement is successful and well tolerated in the majority of patients and should be considered for patients receiving IP P32.

Adult↗
PubMed1987

Bronchocarcinogenic properties of welding and thermal spraying fumes containing chromium in the rat.

The possible bronchocarcinogenic effects of fumes released during the shielded metal arc welding of stainless steel and the thermal spraying of chromium oxide (Cr2O3) have been studied on the rat. The fume particles were shown to contain tri- and hexavalent chromium in soluble and low soluble forms; they were collected and implanted as pellets in the bronchi of groups of 100 rats by the method of Laskin et al. A negative control group of 100 rats was included, as well as positive controls receiving pellets containing benz(a)pyrene. The experiment was continued for 34 months; no differences of biological significance were noted between the growth rates, survival times, and terminal organ weights of the test and negative control groups. At autopsy, the macroscopic and microscopic appearance of the organs in the three groups, including the local reaction to the implanted pellet, were similar. No precancerous changes were observed at the implantation sites; one rat, who received a pellet containing welding fumes, showed squamous cell carcinoma remote from the implantation site and not associated with the bronchus. It had the appearance of a metastasis. All three benz(a)pyrene control rats developed cancer at the implantation site. The occupational health implications of these findings are discussed.

Air Pollutants, Occupational↗