Cytogenetic interactions of contrast media and antineoplastic drugs

The cytogenetic interactions of ionic (diatrizoate, ioxaglate) and nonionic (iohexol) contrast media (CM) with antineoplastic drugs cyclophosphamide (CPA) and carmustine (CARM) were evaluated in a rat bone marrow cell model. Male Wistar rats were anesthetized with a 6% chloral hydrate solution and divided into five groups of five rats each. In protocol 1, three groups of rats received diatrizoate, ioxaglate, and iohexol (2.5 mL/kg) intravenously within 30 seconds. The remaining two groups were similarly injected with CPA and CARM (10 mg/kg). Control animals were injected with nonpyrogenic sterile water or saline solution. After 12 and 24 hours, the animals were killed with an overdose of chloral hydrate, and bone marrow smears were prepared for determining chromosomal damage in polychromatic erythrocytes (PCEs) by a micronucleus test. In protocol 2, CPA and CARM were injected, and 15 minutes later, bolus injections of diatrizoate, ioxaglate and iohexol were given through the same route. Both ionic and nonionic CM induced significant numbers of micronuclei in PCEs (P less than .05). CPA caused a severe cytogenetic effect, whereas CARM did not produce a significant number of micronuclei in PCEs compared with control. In protocol 2 experiments, antagonism with CPA and synergism with CARM was demonstrable. Clinical implication of the cytogenetic interactions between CM and antineoplastic drugs remains to be established.