Robert K. Breger

Pulmonary toxicity, hepatic, and extrahepatic metabolism of 2-methylnaphthalene in mice

Abstract Male mice ( C57BL 6J ) were injected once ip with 0.1, 1, 100, 200, 400, 600, 800, or 1000 mg/kg of 2-methylnaphthalene dissolved in corn oil. After 24 hr, the animals were killed and the lungs, livers, and kidneys were prepared for light microscopy. In addition, some lungs were subjected to scanning and transmission electron microscopy. A dose of 200 mg/kg produced a bronchiolar necrosis which affected the nonciliated bronchiolar (Clara) cell; the parenchymal cells remained unaffected. At higher doses of 2-methylnaphthalene (800 mg/kg), in addition to the damaged Clara cell, severe damage to the upper respiratory tract was noted. No liver or kidney pathology was detected by light microscopy in animals treated with the highest dose. No cellular damage was noted in any organ at doses less than 200 mg/kg. Forty-eight hours after a dose of 200–1000 mg/kg of 2-methylnaphthalene, less pulmonary damage was detected by light microscopy. The metabolism of 2-methylnaphthalene was investigated in hepatic, pulmonary, and renal microsomes from C57BL 6J mice. Lung and liver microsomes produced three isomeric dihydrodiols of 2-methylnaphthalene as well as other monohydroxylated metabolites. Only trace amounts of these metabolites were produced by the kidney.

Comparative effects of hexachloro- and hexabromobenzene on hepatic monooxygenase activity of male and female rats.

Male and female Sprague-Dawley rats were treated once with either crude or purified hexachlorobenzene (HCB) or crude or purified hexabromobenzene (HBB) at 150 mg/kg, intraperitoneally. Examination of hepatic microsomes 4 d later revealed an increase in cytochrome P-450 levels in both HCB- and HBB-pretreated animals. HBB produced a slight but statistically significant hypsochromic shift. Both HCB and HBB produced an increase in benzphetamine N-dealkylation: HCB produced a greater effect than HBB, and male rat microsomes produced more HCHO than female rat microsomes from the N-demethylation of benzphetamine. HCB and HBB both enhanced ethoxycoumarin and ethoxyresorufin O-dealkylation. Liver-to-body weight ratios were not significantly affected by pretreatment with either halogenated compound. There appeared to be no difference between the crude and purified halogenated compounds. Electrophoresis of microsomes from male rats pretreated with purified HBB indicated the presence of a band at 53,000 daltons, which was also seen in microsomes from rats pretreated with 3-methylcholanthrene. This band was absent in microsomes from rats pretreated with phenobarbital. Evidence from other laboratories has demonstrated the mixed type of P-450(s) induction after HCB administration, as does this report using enzymic and electrophoretic data.

T1, T2 and proton density measurements in the grading of cerebral gliomas

The possibility that cerebral tumours may be graded by measuring T1 or T2 with magnetic resonance (MR) imaging was studied. A consecutive series of patients with subsequently verified gliomas was enrolled, and studied with MR. Patients who had prior surgical, chemotherapeutic or steroid treatment were excluded. Single slice multiple saturation recovery and multiple spin echo techniques were used to measure T1, T2 and proton density in the tumour. In 33 patients with cerebral gliomas there were 5 grade I, 12 grade II, 7 grade III and 9 grade IV. T1 and T2 values tended to be smaller in grade I gliomas than in grades II, III and IV gliomas. Relaxation parameters overlapped considerably in tumours with different grades. Proton density values did not show much change between different grades of gliomas. Relaxation parameters cannot be used to determine tumour grade reliably.