Tumours and malformations in the adult offspring of cyclophosphamide-treated and control male rats — Perliminary communication

Francis, Anne J.; Anderson, Diana; Evans, J.G.; Jenkinson, P.C.; Godbert, P.

doi:10.1016/0027-5107(90)90097-n

Cited by 17 publications

(16 citation statements)

References 13 publications

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“…It is well established that genotoxic effects lead to induction of cancer, reduced fertility and heritable diseases. [7][8][9] In the present study, we used the occurrence of micronuclei (MN) in exfoliated buccal and bladder cells of khat consumers to obtain information on genotoxic effects and on possible carcinogenic risks in humans. MN are extranuclear chromatin bodies in the cytoplasm formed when chromosome fragments or whole chromosomes are not incorporated into daughter nuclei during mitosis.…”

Section: Abstract: Khat; Buccal Mucosa; Micronuclei; Aneugenmentioning

confidence: 99%

“…10 MN formation is used to identify genotoxic effects of chemicals in a variety of in vitro and in vivo test procedures. 8,11 MN assays with exfoliated cells from oral cavity, bladder, cervix or endometrium 12 have been used successfully to detect DNA damage and possible cancer risks caused by endogenous and exogenous factors in humans. These organs are frequent sites of tumor formation.…”

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Khat (Catha edulis) consumption causes genotoxic effects in humans

Kassie

Darroudi

Kundi³

et al. 2001

Int. J. Cancer

123

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We used the micronucleus (MN) test to determine the genetic damage caused by khat, a widely consumed psychostimulant plant, in exfoliated cells of volunteers who chewed the drug on a regular basis. In the first study in which we compared the frequency of MN in buccal and bladder mucosa cells in 20 khat consumers (10 -160 g/day) and 10 controls, a pronounced (8-fold) increase in micronucleated buccal mucosa cells was seen among khat consumers; khat consumption did not lead to a detectable elevation of micronucleated bladder mucosa cells. Among heavy khat chewers, 81% of the MN had a centromere signal indicating that khat is aneuploidogenic. To investigate the effect of simultaneous consumption of tobacco and alcoholic beverages, we compared the MN frequency in buccal cells of 25 khat consumers (20 -85 g/day) who smoked cigarettes (15-60/day) and drank alcoholic beverages (15-80 g of pure ethanol/day) with a control group (control group I) of 25 individuals matched for age, body weight, tobacco and alcohol consumption and with another control group of 25 individuals (control group II) not consuming any of the drugs. The frequency of buccal mucosa cells with MN was higher in control group I than in group II and the effect of khat, tobacco and alcohol was found to be additive. A time-kinetics study on khat-induced MN showed that the highest frequency of MN was observed during the fourth week after consumption. In light of the large body of evidence on the close association between genetic damage and cancer, these results suggest that khat consumption, especially when accompanied by alcohol and tobacco consumption, might be a potential cause of oral malignancy. © 2001 Wiley-Liss, Inc. Key words: khat; buccal mucosa; micronuclei; aneugenThe habit of khat chewing has prevailed for centuries among populations in the horn of Africa and the Arabian peninsula. The leaves of Catha edulis (commonly termed as q'at or khat) contain the natural amphetamine cathinone, which has euphoric and psychostimulant effects. 1,2 Due to its widespread consumption, the production of khat has become an important economic factor. Apart from coffee, khat is the largest cash crop in Yemen and Ethiopia. 3 It has been estimated that in Somalia and Yemen up to one-third of the family income is spent on chewing khat 2 and about 80% of the adult population of these countries are consumers of khat. In Yemen, approximately US$700 million are spent on khat, and in Somalia the annual expenditure for the khat import is about US$57 million.Toxic effects of khat in humans have been studied over the last 20 years and include multiple symptoms such as euphoria, anorexia, insomnia, gastritis, hypertension and impotence. 4 In bacteria, crude khat extract caused gene mutations and cathinone and crude khat extract induced structural chromosomal aberrations 5 and MN formation 6 in bone marrow cells of mice. However, no data on the potential genotoxic effects of khat in humans are available. It is well established that genotoxic effects lead to induction of cancer...

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Section: Abstract: Khat; Buccal Mucosa; Micronuclei; Aneugenmentioning

confidence: 99%

mentioning

confidence: 99%

Khat (Catha edulis) consumption causes genotoxic effects in humans

Kassie

Darroudi

Kundi³

et al. 2001

Int. J. Cancer

123

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“…By using this type of study design, we have examined the following compounds using chronic and acute exposure: cyclophosphamide, 1,3-butadiene and urethane (ethyl carbamate) ( Table 1). [42][43][44][45][46][47][48][49] Cyclophosphamide was positive for all endpoints in the rat after chronic gavage exposure. 43,44 This effect has also been shown by others 45 and led to the belief that chronic exposure might be a more realistic model than acute exposure, as man is chronically exposed in the workplace and environmentally.…”

Section: Paternal Exposure To Chemicalsmentioning

confidence: 99%

“…[42][43][44][45][46][47][48][49] Cyclophosphamide was positive for all endpoints in the rat after chronic gavage exposure. 43,44 This effect has also been shown by others 45 and led to the belief that chronic exposure might be a more realistic model than acute exposure, as man is chronically exposed in the workplace and environmentally. The colorless gas 1,3-butadiene also induced congenital malformations and was significant in mice in one 46 but not in another, 47 with no increase in tumors after subchronic inhalation exposure.…”

Section: Paternal Exposure To Chemicalsmentioning

confidence: 99%

“…They can be measured and scored in the same way as teratogenic defects after in utero exposure of females. [42][43][44][46][47][48][49] A1b: If delayed effects in the offspring are considered as childhood cancers, cognitive developmental defects, growth disorders and the like, then in humans after radiation it was thought that exposed fathers had given rise to leukemia in their children. 63,64 However, the case was thrown out of court because it foundered on 'the balance of probabilities' .…”

Section: Questions From the Panel Q1mentioning

confidence: 99%

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