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Biomedical subjects

J R Cabral

Publications and source records attributed to J R Cabral.

At least 55 records · Page 3Linked to original sources

Effects of long-term intake of DDT on rats.

DDT is a pesticide used in malaria-control programmes throughout the world. Its potential carcinogenicity was studied in MRC Porton rats (Wistar-derived) which received dietary concentrations of 0, 125, 250 and 500 parts per million DDT (technical-grade) for life. The treatment had no adverse effects on body growth or survival rate. Various types of tumours were observed in animals in all groups: exposure to DDT resulted in statistically significant increased incidence of liver-cell tumours only in female treated rats; one such tumour was observed in control rats. No metastases of these tumours were found.

Animals↗

Carcinogenicity study of the pesticide maleic hydrazide in mice.

The carcinogenicity of the pesticide maleic hydrazide (MH) was studied in C57BL/B6 mice. After subcutaneous (s.c.) administration no significant increase in the incidence of liver-cell tumours was seen over that in solvent-treated controls, and although a statistically significant difference in the incidence of liver-cell tumours was observed between treated and untreated males, this was considered biologically inadequate as evidence of carcinogenic effect. When MH was administered orally, no significant increase in the incidence of liver-cell tumours was seen. These results partially confirm the negative finding of a recent parallel study in rats [1].

Administration, Oral↗

Carcinogenicity of some pyrrolic pyrrolizidine alkaloid metabolites and analogues.

Repeated topical doses of dehydromonocrotaline, a putative primary toxic metabolite of the pyrrolizidine alkaloid monocrotaline, followed by repeated treatments with croton oil, produced malignant tumours of the skin in LACA mice. A chemically similar alkylating agent, 2,3-bistrimethylace-toxymethyl-1-methylpyrrole, was carcinogenic without use of a promoter, confirming a preliminary report. Its high activity was due to the intact ester, not to its hydrolysis products. Dehydroretronecine (DHR), a less reactive secondary metabolite of monocrotaline, was also carcinogenic to LACA mouse skin, but it was less active than previously reported in experiments with another strain. Similar carcinogenicity was shown by the synthetic 2,3-bishydroxymethyl-1-methylpyrrole, but not by 2,3-bis-hydroxymethyl-5-methyl-1-phenylpyrrole, which has a high level of antimitotic activity.

Alkaloids↗

Increased cancer incidence in the progeny of male rats exposed to ethylnitrosourea before mating.

Results from previous experiments have indicated tha persistence of an increased cancer risk in subsequent generations following prenatal exposure to a chemical carcinogen. In the present experiment, the possible role of prezygotic events in determined cancer risk was investigated in the progeny of male rats treated with ethylnitrosourea (ENU) before mating with untreated females. Eight BDVI male rats were given a single i.p. dose of 80 mg/kg bw ENU and each rat was then caged at weeks 1, 2, 3 and 4 after treatment with three untreated females. Fertility was lower and preweaning mortality higher in the experimental group, as compared to controls, particularly at the 4th-week mating. Survival rates after weaning were similar in the progeny of treated males and controls, as was the total incidence of tumours. However, analysis of tumour incidence at the various organ sites showed an increased incidence of neurogenic tumours in the progeny of ENU-treated males, as compared to that of controls.

Animals↗

Carcinogenicity study of 3-(5-nitro-2-furyl)-imidazo(1,2-alpha) pyridine in mice and rats.

3-(5-nitro-2-furyl)-imidazo(1,2-alpha) pyridine was tested for carcinogenicity by long-term administration in the diet to CTM mice at 0.1, 0.2 and 0.4% dose levels and to Wistar rats at 0.2 and 0.4% dose levels, and by short-term intraperitoneal injections to suckling BALB/c mice. The compound was a strong carcinogen. In CTM mice it induced carcinomas of the esophagus and forestomach at all dose levels and thymic lymphosarcomas at the two highest doses. In male and female rats, esophagus and forestomach papillomas were observed at all dose levels, whereas esophagus and forestomach carcinomas and kidney tumors were observed only at the high dose. In female rats, an increased incidence of mammary tumors was seen at the high dose. The treatment of BALB/c suckling mice by intraperitoneal injections did not induce a clear carcinogenic response.

Age Factors↗

Liver-cell tumours in rats fed hexachlorobenzene.

All animals in a group of female Agus rats fed 100 ppm of hexachlorobenzene (HCB) in their diet for up to 90 weeks developed multiple liver-cell tumours whereas none were seen in control rats. There was no evidence of skin lesions or nervous symptoms usually seen with higher doses of HCB. A high incidence of liver-cell tumours was also seen with MRC Wistar female rats fed HCB for 75 weeks.

Animals↗

Effect of partial hepatectomy on the response of rat liver to aflatoxin B1.

The effect of partial hepatectomy (PH) on aflatoxin B1 (AFB1) action in rat liver has been examined using adult male Fischer 344 rats. The elevated levels of hepatic DNA synthesis, present 26 hr after PH (> 15 times the control level) and 33 hr after PH, are rapidly inhibited by i.p. administration of AFB1. The percentage inhibitions are greater than those observed using intact or sham-operated animals. However, it was possible to demonstrate elevation of DNA synthesis in PH rats treated with AFB1. Rats 2 hr after being treated with AFB1 (0.075 mg/kg) at 24 and 31 hr after PH exhibited levels of DNA synthesis 380 to 400% of those present in sham-operated uninjected controls. After 62 weeks, the livers of the PH rats treated with AFB1 displayed no hepatocellular carcinoma. There was present, however, an increased incidence of lesions believed to be preneoplastic. The differences between the long-term effects of AFB1 and other hepatocarcinogens on the livers of PH rats are discussed in terms of their relative capacities and modes of action in inhibiting DNA synthesis.

Aflatoxins↗

Effects of some pyrrolic and dihydropyrrolizine esters on mouse skin: a preliminary study.

Groups of male BALB/c mice were given 33 to 35 treatments during 52 to 54 weeks with 5 ester alkylating agents. Two of these (I and II) were potential metabolites of carcinogenic pyrrolizidine alkaloids; the others (III-V) were chemically similar synthetic compounds. Each dose of 0.5 or 1.0 mumol, in acetone, was applied to the shaved dorsal skin. A control group received acetone. Three skin tumours and 2 preneoplastic lesions were found among 9 mice receiving the compound IV, the agent giving the slowest chemical alkylation reactions. No skin tumours were seen in the other groups. The results suggest that the relationship between carcinogenic potential and alkylating reactivity in this series of compounds should be further investigated.

Alkylating Agents↗

A difference between two strains of rats in their liver non-haem iron content and in their response to the porphyrogenic effect of hexachlorobenzene.

Female Agus rats developed hepatic porphyria at a much faster rate than female Porton-Wistar rats when fed a diet containing 0.01% of hexachlorobenzene (HCB). They also showed a greater inhibition of liver uroporphyrinogen decarboxylase [EC 4.1.1.37] activity and a marked stimulation of 5-aminolaevulinate synthetase [EC 2.3.1.37]. The difference between the two strains could not be correlated with differences in the liver concentrations of HCB. However, control Agus rats were found to possess significantly higher levels of total non-haem iron in their livers than the Porton animals. This was particularly apparent after 24 h of starvation and is further evidence for the involvement of iron in the pathogenesis of HCB-induced porphyria. The posterior lobes of the livers from the Agus rats given HCB became porphyric more slowly than the remainder with less severe inhibition of uroporphyrinogen decarboxylase. In contrast to their increased susceptibility to HCB, the Agus rats were less susceptible to another prophyrogenic agent, 3,5-diethoxycarbonyl-1,4-dihydrocollidine.

5-Aminolevulinate Synthetase↗

A carcinogenicity study of pesticide dieldrin in hamsters.

Syrian golden hamsters were fed for their lifespan a diet containing 0, 20, 60 and 180 parts per million (ppm) Dieldrin. Tumour-bearing animals totaled 13% among control females and ranged between 3-15% in treated females. Eight per cent of male controls had tumours and between 16-23% of treated males. Incidences of endocrine organ tumours were comparable in all groups. A hepatoma was found in 1 female and 1 male led 180 ppm Dieldrin. The present results show that hamsters tolerate higher doses of Dieldrin than do mice and rats. No significant tumour incidence was observed in treated versus control Syrian golden hamsters.

Animals↗

The roles of age at treatment and dose in carcinogenesis in C3Hf/Dp mice with a single administration of N-nitroso-N-methylurea.

C3Hf/Dp mice were given a single i.p. injection of 50, 25 or 5 mug/g N-Nitroso-N-Methylurea (NMU) at either 1 or 70 days of age or 50 mug/g at 21 days of age. They were observed until death or until 120 weeks of age. The two highest doses of NMU produced tumours in a wide spectrum of organs, including the thymus, forestomach, lung, liver (only in males), kidneys, ovaries and orbital glands. The only two tumour types which appeared to be closely related to the occurrence of death were thymic lymphomata (most of which were found in mice dying before 40 weeks after treatment) and carcinomata of the forestomach. Lifetime analyses are presented concerning the occurrence of these two tumour types as well as the occurrence of any tumour after 40 weeks of age or since treatment. Incidences of thymic lymphomata were 67.6%, 39.0% and 21.2% in mice receiving 50 mug/g NMU at 1, 21 and 70 days respectively and 17.1% in mice receiving 25 mug/g at 1 day. In the other groups the incidence of thymic lymphomata was zero or negligible. The rate of progression of thymic lymphomata until death was related to both earliness of treatment and dose. On the contrary, incidences and progression of carcinomata of the forestomach were unrelated to age at treatment. Since breakdown of NMU is very rapid and does not require enzymes, these results are considered as evidence that host-tumour interaction differs from organ to organ. No excess of tumours over the controls was found in mice receiving 5 mug/g either at 1 or 70 days of age.

Age Factors↗