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I L S E
L A S N I T Z K I
animals. The failure of the hormone to stimulate the young epithelium
may be due to differences in susceptibility of the strain of mice used or
to differences in the composition of the medium; thus, that used by
Franks may have contained larger amounts of oestrogenic hormones,
which would increase the total concentration of the hormone. The use
of a defined hormone-free medium in place of the biological medium
might decide this point and also explain the different effects seen after
testosterone treatment by the two authors.
(e) The influence of oestrone on precancerous changes. Oestrogens used in
the therapy of prostatic cancer in man cause a temporary regression
of primary and secondary tumours (Huggins, Scott and Hodges, 1941;
Kahle, Schenken and Burns, 1943). In experimentally induced glandular carcinomata of the prostate of young mice, treatment with
oestrogens or orchidectomy retarded tumour growth (Horning, 1949).
On the other hand, oestrogens applied together with methylcholanthrene during carcinogenesis accelerated and increased the production
of squamous prostatic tumours (Horning, 1952).
20-Methylcholanthrene added to the medium of mouse prostate
glands directly induces a striking hyperplasia and squamous metaplasia of the alveolar epithelium in glands from all ages (Lasnitzki,
1951, 1955b). Addition of oestrone modified the carcinogen effect
(Lasnitzki, 1954) in young glands along the lines described by Horning
(1949, 1952). Simultaneous application of the two compounds accelerated and increased squamous metaplasia while administration of the
hormone to explants previously treated with methylcholanthrene
caused a widespread destruction of the hyperplastic epithelium, either
before or after squamous transformation had taken place. In the former
the cells enlarged, the cytoplasm became vacuolated and the nuclei
pycnotic; in the latter, squamous cells and precornified elements were
shed, leaving empty alveoli behind (Lasnitzki, 1954) (Figs. 21 and 22).
This degeneration closely resembled that observed by Horning (1949)
in induced carcinomata of the mouse prostate following treatment with
stilboestrol and also those seen by Fergusson and Franks (1953) in
human prostatic cancer following oestrogen therapy. This similarity in
effect suggests that the hormone affects the cancer cells directly,
although an additional indirect action via the pituitary and other
endocrine glands cannot be excluded.
In older explants, simultaneous application of hormone and carcinogen produces a similar pattern of response to that seen after the hormone alone: inhibition of epithelial growth and stimulation of the
stroma. In such doubly treated cultures epithelial hyperplasia is
greatly reduced as compared with that seen in explants exposed to the
carcinogen alone, and the fibromuscular stroma considerably in-
I L S E
L A S N I T Z K I
animals. The failure of the hormone to stimulate the young epithelium
may be due to differences in susceptibility of the strain of mice used or
to differences in the composition of the medium; thus, that used by
Franks may have contained larger amounts of oestrogenic hormones,
which would increase the total concentration of the hormone. The use
of a defined hormone-free medium in place of the biological medium
might decide this point and also explain the different effects seen after
testosterone treatment by the two authors.
(e) The influence of oestrone on precancerous changes. Oestrogens used in
the therapy of prostatic cancer in man cause a temporary regression
of primary and secondary tumours (Huggins, Scott and Hodges, 1941;
Kahle, Schenken and Burns, 1943). In experimentally induced glandular carcinomata of the prostate of young mice, treatment with
oestrogens or orchidectomy retarded tumour growth (Horning, 1949).
On the other hand, oestrogens applied together with methylcholanthrene during carcinogenesis accelerated and increased the production
of squamous prostatic tumours (Horning, 1952).
20-Methylcholanthrene added to the medium of mouse prostate
glands directly induces a striking hyperplasia and squamous metaplasia of the alveolar epithelium in glands from all ages (Lasnitzki,
1951, 1955b). Addition of oestrone modified the carcinogen effect
(Lasnitzki, 1954) in young glands along the lines described by Horning
(1949, 1952). Simultaneous application of the two compounds accelerated and increased squamous metaplasia while administration of the
hormone to explants previously treated with methylcholanthrene
caused a widespread destruction of the hyperplastic epithelium, either
before or after squamous transformation had taken place. In the former
the cells enlarged, the cytoplasm became vacuolated and the nuclei
pycnotic; in the latter, squamous cells and precornified elements were
shed, leaving empty alveoli behind (Lasnitzki, 1954) (Figs. 21 and 22).
This degeneration closely resembled that observed by Horning (1949)
in induced carcinomata of the mouse prostate following treatment with
stilboestrol and also those seen by Fergusson and Franks (1953) in
human prostatic cancer following oestrogen therapy. This similarity in
effect suggests that the hormone affects the cancer cells directly,
although an additional indirect action via the pituitary and other
endocrine glands cannot be excluded.
In older explants, simultaneous application of hormone and carcinogen produces a similar pattern of response to that seen after the hormone alone: inhibition of epithelial growth and stimulation of the
stroma. In such doubly treated cultures epithelial hyperplasia is
greatly reduced as compared with that seen in explants exposed to the
carcinogen alone, and the fibromuscular stroma considerably in-