801

Limonene trial in cancer

A phase I trial of limonene in pancreaticand colorectal cancer is planned to start thisweek at Charing Cross Hospital in London,UK. Prof Charles Coombes’ group willenrol up to 30 patients who are refractory tocurrent best treatment in an oral dose-

escalating regimen. :

Limonene, a simple monoterpene,occurs naturally in many plant oils, includ-ing extracts from orange peel and othercitrus fruits, and in mint and in dill,caraway, and celery seed oils. Its anti-

tumour effect with low toxicity was firstreported in rodent models in 1984 byMichael Gould’s group at the University ofWisconsin’s cancer centre in Madison,Wisconsin. :

In rodent models, limonene and deriva-tives inhibit tumour formation and causetumour regression. Two mechanisms ofaction are being actively studied. First, incell culture, limonene and perillyl alcohol(an extract from lavender oil) inhibit thepost-translational isoprenylation of smallG proteins (21-26 kDa), which includemembers of the ras group of signal-transduction proteins that are implicated incarcinogenesis. Disruption of isoprenyl-ation prevents cellular localisation andhence protein function.

The second is an intriguing mechanismin a rat mammary tumour model thatGould and co-workers, together withRandy Jirtle from Duke University, havebeen investigating.’ 1 Transforming-growth-factor pi (TGF-&bgr;l) is a potentmitoinhibitor, but is normally latent. Thiscompound can be activated by binding tothe mannose-6-phosphate/insulin-like-growth-factor-II (M6P/IGF-II) receptor, vwhich also degrades IGF-11, a potentmitogen. Cells from tumours in regressionafter treatment with limonene had substan-

tially increased concentrations of TGF-&bgr;l : vand of M6P/IGF-II receptor. Tumours :that did not respond to limonene did notoverexpress M6P/IGF-II. The gene for this receptor is maternally

: imprinted and hence hemizygous. Modifi-: cation of the one expressed allele of this: gene could prevent terpene-induced up-: regulation. Drugs that interact with the M6P/IGF-II receptor may represent a

novel class of anticancer agent. One possi-: bility, says Jirtle, is the de-repression of the

allele inactivated during imprinting.

David McNamee

1 Jirtle RL, Haag JD, Ariazi EA, Gould MN.Increased mannose 6-phosphate/insulin-likegrowth factor II receptor and transforminggrowth factor &bgr;1 levels during monoterpene-induced regression of mammary tumours.Cancer Res 1993; 53: 3849-52.

Integrated environmental control

Reports that Britain and France are seekinga relaxation of European Communitydrinking and bathing water quality stand-ards suggest that the EC is embarked onwhat environmentalists fear will developinto a "renationalisation" of environmentpolicy. Now EC Environment Commis-sioner loannis Paleokrassas wants to halt

the stream of detailed EC directives dealingwith specific pollutants such as titaniumdioxide or asbestos-or with separatemeasures on water or air quality. Instead,the new directive seeks "a balanced systemfor reduction of emissions from industrialinstallations into the air, water and soil"through a regimen of "integrated pollutionprevention and control". Specified types ofindustrial plant would have to satisfy pollu-tion prevention requirements to qualify fora ten-year operating licence. Member stateswould enjoy some discretion in settingemission limit values and technical require-ments, subject to supervision fromBrussels. :Some states have already begun taking an

integrated approach to pollution control,led by Denmark, France, and Luxem-bourg, followed by Ireland and the UK. :

Arthur Rogers

Insensitive advertisements

The AFLS (Agence francaise de lutte :contre le sida), a French paragovernmentalorganisation, has taken legal action to banadvertisements in Benetton’s latest adver-

tising campaign in the press and on

billboards. The advertisements show partsof the human body tattooed with the words"HIV positive". AFLS declares that thecampaign makes use of degrading imagesand exploits suffering and disease forcommercial ends. Other sickness-relatedorganisations are equally outraged by the v

connection between HIV-infected indivi-duals and butcher’s meat and by the refer-ence to tattooed victims of Nazi concentra-

tion camps. French newspapers have not

accepted the advertisements. :The legal action will have negligible

effect since the campaign will be finishedby the time the tribunal announces itsdecision. Some people complain that theAFLS has merely supplied Benetton withadditional publicity. Replying to the v

French government, Benetton draws atten-tion to its various initiatives for preventionof AIDS (in France as well) and maintainsthat its aim was to underline the dangers ofstigmatisation and of excluding minorities.

Jean-Yves Nau

News in brief

Laparoscoplc surgery Three centres atwhich surgeons may train to do minimallyinvasive therapy are to be set up in theUK-at the Royal College of Surgeons(London), St James’ University Hospital(Leeds), and Ninewells Hospital (Dundee).They will be funded by ;E2 million from thegovernment and ,E2 million from the Wolf-son Foundation charity.

Genetic modlficatlon of food The UK

government has accepted the recom-

mendations of its Ethical Committee onGenetic Modification of Food subject toreview of labelling issues by the FoodAdvisory Committee. The recom-

mendations include the discouragement ofthe unnecessary use of "ethically sensitive"genes; the provision of information to thepublic, on food labels or by other means,that a food product contains genes of alienorigin or has been genetically modified; andincreasing public understanding of the

process of genetic modification.

HIV compensation Canadian provinces(except Nova Scotia, which earlier this yearunveiled a more generous package [LancetJuly 3, p 40]) are now offering individualswho acquired HIV infection through bloodtransfusion a Can$139 million compensa-tion package provided they waive their

right to sue the provinces, hospitals, andthe Canadian Red Cross Society and itsinsurers.

Research funds The Canadian

government has pledged to restore partlythe funding of the National Centres ofExcellence programme to a level of Can$192 million over 4 years, after havingdecided earlier this year to slash fundingfrom$240 million over 5 years to$125million over 4 years (see Lancet Sept 4p 606).

HCV test kits The French Ministry ofHealth has withdrawn four hepatitis C testkits on the basis of sensitivity testing duringthe seroconversion phase of the infection.The tests are Virelli Diagast, EnzygnostBehring, Organon Teknika, and Well-

cozyme.

: Listeriosis Pork rillettes have been con-firmed as the source of the listeriosis

epidemic that arose in Brittany, France,two months ago (see Lancet Sep 4, p 607),during which 35 cases (4 abortions) werereported. The Pasteur Institute is trying tofind out why this usually non-pathogenicstrain has now acquired an epidemic

potential.